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Tomoscintigraphie myocardique double-isotope(¹23I/99mTc) sur gamma-caméra à semi-conducteur :
aspects méthodologiques et applications cliniquesTanguy Blaire
To cite this version:Tanguy Blaire. Tomoscintigraphie myocardique double-isotope (¹23I/99mT c) sur gamma-caméra àsemi-conducteur : aspects méthodologiques et applications cliniques. Médecine humaine et pathologie.Normandie Université, 2017. Français. �NNT : 2017NORMC418�. �tel-01693259�
THESE
Pourobtenirlediplômededoctorat
SpécialitéRechercheclinique,innovationtechnologique,santépublique
Préparéeauseindel’UniversitédeCaenNormandie
Tomoscintigraphiemyocardiquedouble-isotope(123I/99mTc)sur
gamma-caméraàsemi-conducteur:aspectsméthodologiquesetapplicationscliniques.
Présentéeetsoutenuepar
TanguyBLAIRE
ThèsedirigéeparMonsieurleProfesseurAlainMANRIQUE,laboratoireSignalisation,
électrophysiologieetimageriedeslésionsd’ischémie-reperfusionmyocardique
SEILIRM
Thèsesoutenuepubliquementle26/09/2017
devantlejurycomposéde
MadameClaudeHOSSEIN-FOUCHERMaîtredeConférences,CHULille
UniversitéLille2Examinateurdethèse
MadameLaetitiaIMBERTPhysicienne,PhD,CHUdeNancy
UniversitédeLorraine,INSERM,UMR-947NancyExaminateurdethèse
MonsieurDenisAGOSTINI
ProfesseurdesUniversités,HDR,
CHUdeCaen,EA4650,UniversitéCaenNormandie
Examinateurdethèse
MonsieurAlainMANRIQUEProfesseurdesUniversités,HDR,
GIPCYCERON,UniversitéCaenNormandieDirecteurdethèse
MonsieurDimitriPAPATHANASSIOUProfesseurdesUniversités,HDR,
InstitutGodinot,UniversitédeReimsRapporteurdethèse
MonsieurFrançoisROUZETProfesseurdesUniversités,HDR,
CHUParis-Bichat,UniversitéParis-DiderotRapporteurdethèse
I
REMERCIEMENTS
Cetravailaétéeffectuédansl’unitéEA4650duGIPCycéronetlesservicesdemédecine
nucléaireduCHUdeCaenetdel’HôpitalPrivéLeBois.Ils’estdérouléenparallèled’uneactivité libéraledemédecinenucléaireàLille. Je tiensà remercier leséquipesquiont
permisetaccompagnéscetravail:MrleProfesseurAlainManrique,Directeurdel’EA4650,Investigationchezl’homme–GIP
Cycéron,MédecinNucléaireauCHUdeCaen,mondirecteurdethèse.Je te remercie sincèrement d’avoir accepté la démarche saugrenue d’un médecin
nucléaire installé en libéral te sollicitant pour commencer une thèse d’université. Tagentillesse, ta mansuétude, ta rigueur intellectuelle, ta disponibilité et tonaccompagnement, ont été un phare tout au long de ce travail. Nous avons créé et
développé des liens amicaux et une confiance réciproque, qui ont éclipsé les raresmomentsdedouteconcernant l’aboutissementdecetravail. J’aiénormémentappris,y
compris sur le plan humain. Ce travail constitue ce jour l’une de mes meilleuresexpériencesprofessionnelles(humainementetintellectuellement),etajetélesbasesdenouveauxtravauxàvenir,entrenosdeuxéquipesrespectives.
MrleProfesseurDenisAgostini,ChefduServicedeMédecineNucléaireduCHUdeCaen,
EA4650,pouravoiracceptéd’êtreexaminateurdecetravail.Tonexpériencesurla123I-MIBG,d’auteuretco-auteuraguerriontétéd’unegrandeaidetoutaulongdecetravail.Jesuiscertainqued’autresprojetscommunsànosdeuxéquipesvontnaîtredecetravail.Mr le Professeur Dimitri Papathanassiou, Chef du Service de Médecine Nucléaire de
l’InstitutGodinotdeReimspouravoiracceptéd’être rapporteuret examinateurde cetravail,sois-enremercié.MrleProfesseurFrançoisROUZET,ServicedeMédecineNucléaireduCHUParis-Bichat,INSERMU698,pourm’avoirfaitl’honneurd’êtrerapporteuretexaminateurdecetravail.
Mme le Docteur Claude Hossein-Foucher, MCU-PH, Service de Médecine Nucléaire àl’HôpitalRogerSalengroduCHUdeLillepouravoiracceptéd’examinercetravail.Notreserviceesttoujoursprêtàaccueillirdesinternes,pourpartagernotreenthousiasmedesgamma-camérasàsemi-conducteurs.
Mme le Docteur Laëtitia Imbert, PhysicienneMédicale à l’Hôpital Brabois du CHU deNancy,INSERMUMR-947IADI,pouravoiracceptéd’examinercetravail.Vosarticlesnousontpermisd’avancerdansnotretravail.Jegardeunexcellentsouvenirdemoninter-CHUàNancy,aucoursduqueljemesuisforméàlacardiologienucléaireetàl’IRMcardiaque.
MrleDocteurFayçalBenBouallègue.Unimmensemercidenousavoirsortidel’ornière
envenantàboutdupost-traitementdesacquisitionsdes2èmeet3èmepartiesdecetravail.
II
MesMaîtres:
Mr Le Professeur Jean-Jacques Le Jeune. Vous m’avez accueilli dans votre service deMédecineNucléaireauCHUd’Angers.Votremansuétudeetbienveillanceà l’égarddespatientsetdel’équipemédicaleetparamédicaleontétéunmodèle.MrLeProfesseurOlivierCouturier,pourvotredynamisme.MrLeProfesseurFurber,pourvotreinitiationàlarecherchecliniqueenIRMcardiaque.
Mr Les Professeurs Karcher, Olivier, Marie et le Docteur Wassila Djabala pour votreaccueildansleservicedeMédecineNucléaireduCHUdeNancy,etmaformationenTEP-TDM,encardiologienucléaireetenIRMcardiaque.
MrLeProfesseurFranckSemahetleDocteurMarie-OdileHabert,pourvoscoursàSaclayenneurologienucléaire.JememetsàlaNeurologieNucléaireaprèslasoutenance!
Mes associées les Docteurs Sylvie Petit et Mathilde Thélu pour votre patience, votre
gentillesse et votre bienveillance tout au long de ce travail, y compris lors deschangements impromptusdeplanning,pourretourneràCaeneffectuerdesmanipsouterminerunarticle.LeDocteursDimitriBellevrerencontrélorsdenosséjoursCaennais
etseslonguessoiréesde«manips».C’estunréelplaisirdet’avoirretrouvéensuiteàLille,etdet’accueillirdèsseptembredansnotreéquipeLilloise.LeDocteurAlbanBailliezqui
m’a accompagné tout au long de ce travail : dans les trajets Lille-Caen, les premièresacquisitionsmêmenocturnesdefantômes,lescongrès(mêmeàSNMdeDenver2017!)etlarédactiondenospapiers.Travaillerauquotidienàvoscôtésestunréelplaisir.
Un immense merci aux équipes de Caen et de Lille, plus particulièrement les
manipulateurs radios Lillois (Magalie, Pierre-François, Paolo, Grégory, Clément, sansoublier Aurélie et Christelle, Cindy, Sarah et Clément), les secrétaires (Carole, Sabine,SéverineetVanessa,CarmelaetAudrey)etlescadres(Dominique,Dorothée,MicheletJordane).Vousnousavezaidéàpréparerlesdosesderadiopharmaceutique,programmerlesprotocolesd’acquisitiondesgamma-caméras,lesrecommencer,lesrecommencer,et
encore,aveccuriositéparfois,maistoujoursdanslabonnehumeur.Vousavezsurassurerlesfantômesetnospatients,toujoursavecpatienceetprofessionnalisme.
MerciégalementauxéquipesduGH-ICL,Jean-PhilippeWillem,LaurentPascal,GauthierCalais,SylvestreMaréchaux,Jean-LouisBonnal,FrançoisGrateauetLaurentDelabyetà
l’équipederecherchecliniquepourleurprécieuxconseilsetleuraccompagnement,leDrAmélieLansiaux,LaurèneNoberciak,Jean-JacquesVitiglianoetlePrPierreGosset.
Merci àmes amis de promos : lesDocteurs Emmanuelle Chambenoit-Grardel,HuguesCoevoet,François-XavierGadroyetGauthierDéfossez.
MerciégalementàSébastienHapdey,AdrienRobicetNathanielRoth.
Ettousceuxquej’auraispuoublier…
III
Mesparentsetgrands-parents,parfaitementaimantetmoralementirréprochables.
Vousm’avezdonnélesensdel’effortetdudépassementdesoi.Masœur,Caroline.Tuascontribuéàmavocationdemédecin.Mon frère, le compagnon de toujours. Merci pour tous ces bons moments passés
ensemble,etceuxàvenir,pourtonépouseCarolineetvosadorablesenfants,BaptisteetCamille.
Lesamis,toujoursprésentspourdécompresser,etplusparticulièrementGeo&Delphine,AudeetMax, SylvainetClaire,NicoetSido,HuguesetAlice,Rémi,Antoineet Juliette,
Antho&Babara,OliveetElo,AlexetAurèle,EricetSonia,OlivieretPerrine,AmauryetMarie,Alexandre,sansoublierApplepoursesordinateursrobustes,ASICS,OdloetXsocks
pourlerunning,LesGlénanspourlavoile,NorthpourlekiteetDécathlonpourlesportengénéral.
Parcequ’iln’estpasdebeauxprojetssansêtrebienaccompagné:Nathalie,monépouse,formidable,dèsnotrerencontre.Tugères,dansl’ombre,notrequotidien(ycomprisles
absences répétées à Caen, en congrès ou lors de réunions), ton travail passionnant,l’éducation de nos enfants, les ami(e)s,mes sautes d’humeur et nos congés (liste nonexhaustive)…Nostroisenfants;Madeleine,AugustinetAdèle.C’estunbonheurquotidien
devousvoirgrandiretvousépanouir.Jesuistrèsfierdevous.
Toutseulonvaplusvite;ensemble,onvaplusloin(proverbeafricain)
IV
Tabledesmatières
I. :Introduction..............................................................................................................11. Gamma-caméras:évolution(sensibilité,résolutionspatialeetenénergie)...................12. Scintigraphiemyocardiquedeperfusion...........................................................................13. Scintigraphiemyocardiqued’innervation..........................................................................24. Notreprojetdethèse............................................................................................................4
II. :Semi-conducteurs,gamma-camérasetacquisitionsdouble-isotope..........................6A. LeCZT:delaconversionindirecteàlaconversiondirecte...................................................6B. LaDNM530c.....................................................................................................................10C. LaDSPECT.........................................................................................................................13D. Acquisitionsendouble-isotope.........................................................................................151. Principes.............................................................................................................................152. Artefactsdel’acquisitiondouble-isotope.........................................................................15
III. :Etudesurfantômedynamiquedelafonctionventriculairegauche(99mTc)enprésenced’123I..................................................................................................................18
A. Résumé.............................................................................................................................18B. Publicationcorrespondante(EJNMMIPhysics,2016)........................................................20
IV. :Etudesurfantômeanthropomorphedetorsedelaperfusionmyocardique(99mTc)enprésenced’123I(innervation)........................................................................................30
A. Résumé.............................................................................................................................30B. Publicationcorrespondante(JNuclCardiol,2017).............................................................31
V. :Déterminationdurapportcardiomédiastinaldelafixationd’123I-MIBGlorsd’acquisitionsTEMPdouble-isotope(123I-MIBG/99mTc-tétrofosmine)surunegamma-caméraCZTàcollimationmulti-sténopéechezlespatientsporteursd’insuffisancecardiaque.........................................................................................................................44
A. Résumé.............................................................................................................................44B. Publicationcorrespondante(JNuclMed,2017).................................................................46
VI. :PremièredéterminationdurapportcardiomédiastinalenimagerieCZTcardiaquedouble-isotope(123I-MIBG/99mTc-tétrofosmine)chezlespatientsporteursd’insuffisancecardiaque:l’étudeADRECARD(EurJNuclMedMolImaging2015)..................................64
VII. :Discussion...........................................................................................................65A. Principauxrésultats..........................................................................................................651. EvaluationdelaFEVGenconditiondouble-isotope........................................................652. Evaluationdelaperfusion(99mTc)enconditiondouble-isotope(99mTcet123I)............653. EvaluationduRCMaveclaDNM530c..............................................................................664. EvaluationduRCMaveclaDSPECT..................................................................................67
B. Discussiongénérale...........................................................................................................681. Intérêtdesacquisitionsendouble-isotope......................................................................682. Champd’acquisitionlimitédesgamma-camérasCZT.........................................................69
3. Rapportsdeconcentrationdesisotopes123Iet99mTcenacquisitiondouble-isotope...704. Post-traitementdesacquisitionsdouble-isotope:particularitésdesartefacts............705. Contaminationcroiséedu99mTcdanslephotopicdu123I................................................716. Comparaisondesduréesd’acquisition:gamma-caméraconventionnellevsCZT........71
C. Limitesdenostravaux......................................................................................................721. Valeurréelledesvolumescavitairesinconnue................................................................722. Différencedepost-traitemententrelesdeuxgamma-camérasCZT..............................723. Champd’acquisitionlimitédescamérasCZT...................................................................72
V
4. Irradiationsupplémentairedel’acquisitiondouble-isotope..........................................73
VIII. :Autrestravaux:Évaluationdelafonctionventriculairesurgamma-camérasàsemi-conducteurs.............................................................................................................74
1. EtudesurfantômeetvalidationcliniquevsIRMdel’évaluationdesfonctionsventriculaires
gauchessegmentaireetglobaleutilisantunegamma-caméraàsemi-conducteurCZT(JNucl
Cardiol2014;21:712-22)...............................................................................................................74
2. Etudesurfantômedynamiqueetvalidationcliniquedel’évaluationdelafonction
ventriculairegaucheutilisantdeuxgamma-camérasCZTdifférentesetunegamma-caméraà
collimationcardiofocale(JNuclMed.2016;57:1370-75).............................................................75
3. Etudedelafonctionetdel’asynchronismeventriculairedroitetgauche:comparaisonde
latomoventriculographieisotopiqueàlaventriculographieisotopiqueplanaireavecune
gamma-caméraàsemi-conducteurCZTetavecunegamma-caméraconventionnelle.(Encours
desoumissionauJNC)..................................................................................................................77
IX. :Conclusionetperspectives..................................................................................78A. Conclusion........................................................................................................................78B. Perspectives......................................................................................................................801. Soumissiond’unesynthèsedecetravailencours...........................................................802. Améliorerlepost-traitementdesdeuxgamma-camérasCZT........................................803. Optimiserl’irradiationsupplémentairedel’acquisitiondouble-isotope.......................804. Champd’acquisitionlimitédesgamma-camérasdédiéesauxexplorationscardiaques 80
5. Gamma-caméraàsemi-conducteurCZTgrandchamp....................................................816. PoursuitedelacollaborationLillo-Caenaise....................................................................81
X. :Bibliographie..........................................................................................................82
VI
Listedestableaux
TABLEAU1COMPARAISONDELADNM530CETDELADSPECT................................................................................14
Listedesfigures
FIGURE1PRINCIPESDECONVERSIONINDIRECTEETDIRECTE........................................................................................7FIGURE2SPECTRESENERGETIQUESSURLADNM530C...............................................................................................8FIGURE3IMAGEETSCHEMADELACAMERADNM530C.............................................................................................10FIGURE4CONFIGURATIONDESDETECTEURSCZTDELADNM530C...........................................................................11FIGURE5SPECTREENERGETIQUED’UNESOURCEPONCTUELLED’123I...........................................................................12FIGURE6CAMERADSPECT....................................................................................................................................13FIGURE7FENETRESENERGETIQUESD'ACQUISITIONENTRIPLEFENETRAGE(TEW)......................................................16
Listedesabréviations
g.gammaCZT.tellururedecadmium-zincDNM530c.DiscoveryNM530cFEVG.fractiond’éjectionventriculairegauchekeV.kilo-électron-voltMBq.mégabecquerelMIBG.métaiodobenzylguanidineMLEM.maximumlikelihoodexpectationmaximizationNaI.ioduredesodiumRCM.rapportcardiomédiastinalTEMP.tomoscintigraphied’émissionmono-photoniqueTEW.tripleenergywindowoutriplefenêtrageVTD.volumetélédiastoliqueVTS.volumetélésystolique
1
I. :Introduction
1. Gamma-caméras:évolution(sensibilité,résolutionspatialeetenénergie).
En évolution constante depuis les années 60, les gamma-caméras
conventionnelles,baséessurleprincipedelaconversionindirectemisaupointparHal
Anger,utilisentuncristalscintillant,desphotomultiplicateursetuntraitementdusignal
pourconvertirl’énergieduphotonincidentensignalélectrique.Leursprogrèscontinus
ontaboutiàuncompromisoptimalentresensibilité,résolutionspatiale,etrésolutionen
énergie.
En 2010, les semi-conducteurs utilisant le tellurure de cadmium-zinc (CZT)
révolutionnentlesgamma-camérasenpermettantlaconversiondirectedesphotons.Ces
caméras à semi-conducteurs, dédiées aux explorations cardiaques, possèdent une
résolutionenénergieaméliorée(4à5%versus10%pourlescamérasdeAnger)(1,2).De
nouvellesperspectivesd’acquisitionssimultanéesendouble-isotopedel’123Ietdu99mTc
seprésentent,dontlespicsénergétiquessontproches.Ils’agitrespectivementdel’étude
simultanéedel’innervation,delaperfusion,etdesfonctionsglobaleetsegmentairedu
ventriculegauche.
2. Scintigraphiemyocardiquedeperfusion
Latomoscintigraphied’émissionmono-photonique(TEMP)myocardiqueestune
technique d’imagerie fonctionnelle non invasive qui permet d’étudier, en trois
dimensions,larépartitiondelafixationdanslemyocarded’unradiopharmaceutique.
La synchronisation des acquisitions à l’électrocardiogramme permet une analyse
concomitante de la fonction ventriculaire gauche. C’est-à-dire l’étude de la cinétique
segmentaire,desvolumestélésystolique(VTS)ettélédiastolique(VTD),etdelafraction
d’éjection (FEVG)du ventricule gauche (3,4). Leurs études respectives (FEVG,VTD, et
VTS)utilisantlaTEMPmyocardiqueontétélargementvalidéesetcomparéesàd'autres
techniquesd'imagerie(5,6).
Lesméta-analysesrécentesontconfirmélesexcellentesvaleursdiagnostique(7)
et pronostique de la TEMP myocardique de perfusion (utilisant des
radiopharmaceutiquesmarquésau99mTcoule201Th)(8-10).Lepronosticestfonctionde
2
l’étenduedudéfautdeperfusionmyocardiqueenpost-effort.Au-delàdeuxsegments(sur
dix-sept) d’ischémie, le bénéfice est plus important avec une revascularisation
myocardiquequ’avecuntraitementmédicaloptimal(9,11).
3. Scintigraphiemyocardiqued’innervation
La relation entre la dysfonction du système nerveux cardiaque autonome, la
myocardiopathieetlasurvenued’épisodesd’arythmiecardiaquegraveestétabliedepuis
longtemps (12,13). Les zones « gâchettes », substrat anatomique et mécanisme
déclencheur les plus fréquents d'arythmies ventriculaires sont la présence respective
d’untissucicatriciel(uneséquelled’infarctusdumyocardeoudemyocardite)auseinde
myocarde viable (perfusé), et d’une anomalie du tonus sympathique cardiaque
(dysinnervé) (14-19). Ces zones représentent les cibles idéales d’ablation par radio-
fréquence(20).
L'innervationsympathiquecardiaquepeutêtredirectementétudiée,demanière
non-invasive, avec l’123I-meta-iodobenzylguanidine (123I-MIBG), un analogue de
norépinephrine radiomarqué (21) qui reflète l'intégrité neuronale en visualisant la
recaptureetlarétentiondanslesterminaisonssympathiquescardiaques(22).Desétudes
antérieures,utilisantdesacquisitionsensérieàl’123I-MIBGetau201Tl,ontrapportéque
l'innervationsympathiquemyocardiqueétaitaltéréeaprèsuninfarctusdumyocarde(23-
25). En raison d’une sensibilité élevée du tissu nerveux à l'ischémie, la dénervation
sympathiquerégionaleexcèdel'étenduedudéfautdeperfusion(26).
Le déficit d'innervation sympathique cardiaque évalué par le rapport
cardiomédiastinal tardif (RCM) de fixation de 123I-MIBG (27) est un facteur pronostic
majeur indépendant demort subite et de survenued’événements cardiaques chez les
patientssouffrantd'insuffisancecardiaque,quellequ’ensoitl’étiologie(28-33).UnRCM
inférieur à 1,6 est associé à un risque accru (28). À l'heure actuelle, le calcul duRCM
nécessiteuneimagestatiqueplanaireduthorax.Cettetechniqueestbienstandardiséeet
reproductibleavecunegamma-caméraconventionnelledeAnger(34,35).
Récemment, les gamma-caméras à semi-conducteurs dédiées aux explorations
cardiaquesutilisantdesdétecteursCZTontconsidérablementtransformélaroutinede
3
l'imagerie de perfusion myocardique chez les patients atteints d'une maladie
coronarienneconnueousoupçonnée(36).Cescamérasontunemeilleuresensibilitéde
détection, ce qui entraîne une diminution des temps d'acquisition et des doses
radiopharmaceutiquesinjectées,etunerésolutionenénergieaméliorée,permettantune
meilleure discrimination de l'énergie des photons en imagerie double-isotope.
Cependant,seulesquelquesétudesontévaluéleurexactitudeenimageriedel'innervation
sympathiquedumyocarde(16,17,37,38)etdelaperfusionventriculairegaucheparTEMP
(39-41).
LesdeuxcamérasCZTdisponiblesdanslecommercediffèrentdansleursensibilité
(4foisamélioréesaveclaDNM530cetpresque7foisaveclaDSPECT)etleurrésolution
spatiale(6,7mmavecDNM530cet8,6mmaveclaDSPECT)conduisantàdesimagesde
netteté, de contraste et de rapport signal-sur-bruit différentes (1,40,42) (Tableau 1
ComparaisondelaDNM530cetdelaDSPECT).
Afindeprévenirlamortsubiteetdeprolongerl’espérancedevie,l’implantation
prophylactique d'un défibrillateur automatique implantable est recommandée
(recommandation de classe IB) (43) chez les patients porteurs (i) d’une insuffisance
cardiaqueasymptomatiqueàdysfonctionsystolique(FEVG≤30%)d’origineischémique
(44-47)àplusde40joursaprèsunIDM(48),ou(ii)d’unemyocardiopathiedilatée(FEVG
≤ 30%) asymptomatique d’origine non-ischémique (49,50), sous traitement médical
optimal.Lestauxdemortsubitepararythmieventriculaireetdemortalitétotalesont(i)
significativementréduitsquandl’ischémieestàl’originedel’insuffisancecardiaque(44-
47) ; mais (ii) non significativement réduits dans les autres étiologies d’insuffisance
cardiaque(étudeDANISH(51)).
L’équipeCaennaiseestimpliquéedelonguedatedansl’imageriedel’innervation
adrénergique du myocarde par la scintigraphie à la 123I-MIBG, puissant facteur
pronostique indépendant qui reflète l’activation neuro-hormonale du myocarde
(28,29,52,53,54).
4
4. Notreprojetdethèse.
La disponibilité en routine clinique de deux modèles de gamma-caméra à semi-
conducteursCZTpixélisés,différents,dédiésauxexplorationscardiaques,degéométrie
d’acquisitiondifférente,amotivéetpermiscetravail:
– LacaméraDSPECT(42)(BiosensorsInternational,Caesarea,Israel),installéedans
le service de médecine nucléaire du CHU de Caen, utilise des colonnes de
détecteursCZTmobilesbalayantlevolumeexploré,équipésd’unecollimationde
typeparallèle.
– La caméra Discovery NM 530c (55) (DNM 530c, General Electric Healthcare,
Milwaukee, Wisconsin), installée dans le service de médecine nucléaire de
l’HôpitalPrivéLeBoisdeLille,utilisedesdétecteursCZTimmobiles,équipésd’une
collimationsténopée,convergentversunellipsoïde(axes:18x16cm).
L’objectif de notre travail de thèse, était de répondre à la question suivante :
« l’amélioration de la résolution en énergie des nouvelles gamma-caméras à semi-
conducteur CZT permet-elle, en condition de routine clinique, l’étude simultanée de
l’innervation(123I-MIBG)etdelaperfusion(radiopharmaceutiquesmarquésau99mTc)en
TEMPmyocardiquechezlespatientsporteursd’uneinsuffisancecardiaque?».
Enconditionderoutinecliniqueavec lesdeuxcamérasCZTdisponiblesdans le
commerce(laDNM530cetlaDSPECT),notretravails’estdérouléentroisparties:
(i) Evaluer l'impactde l'acquisitiondouble-isotopesimultanée (123I/ 99mTc)
surl’étudedelafonctionventriculairegaucheglobaleetrégionaledansle
photopicdu99mTc,enutilisantunfantômecardiaquedynamique.
(ii) Comparer les acquisitions cardiaques séparées de 123I (innervation) et
99mTc(perfusion)auxacquisitionsdouble-isotopesimultanées,enutilisant
unfantômeanthropomorphedetorseéquipéd’uninsertcardiaque.
5
(iii) Comparer le RCM tardif de la fixation de l’123I-MIBG, déterminé en
acquisition CZT double-isotope, à celui déterminé en imagerie planaire
conventionnellechezlespatientsporteursd’uneinsuffisancecardiaque.
Afindefaciliterlalecturedecemémoire,lesprincipesdedétection,dereconstruction
etdetraitementdesacquisitionsdeMédecineNucléaireconventionnellesontconsidérés
acquis.
Lapremièrepartieseraconsacréeauxrappelssurlesdétecteursàsemi-conducteurs
CZT équipant les gamma-caméras, à une présentation rapide des gamma-caméras
étudiéesetauxprincipesdereconstructiondesacquisitionsendouble-isotope.
Chaqueétudedenotretravaildethèseseraensuiteintroduitedanssaproblématique,
comporteralesméthodesutiliséesetserasuiviedelapublicationcorrespondante.
Ensuite, une discussion générale détaillera les principaux résultats obtenus dans
chacundesvolets.
Uneconclusiongénéraleouvriravers lesprojetset lesperspectivesquipourraient
fairesuiteàcetravail.
6
II. :Semi-conducteurs,gamma-camérasetacquisitions
double-isotope
A. LeCZT:delaconversionindirecteàlaconversiondirecte
Rappel sur les semi-conducteurs, leurs caractéristiques et les avantagesde leur
utilisationdanslesgamma-caméras
Lesgamma-camérasmisesaupointparAngersontbaséessurdesdétecteursà
scintillationetutilisentlaconversionindirecte.Développéesetperfectionnéesdepuisles
années60,ellesontpermisl’essordelaMédecineNucléaire.Leurslimitesthéoriquesde
sensibilité de détection, de résolution spatiale et en énergie ont été atteintes. Les
industriels ont proposé une nouvelle technologie de détection grâce aux semi-
conducteurs:laconversiondirecte.
Cecourtchapitrerappellelescaractéristiquesdesdétecteursàsemi-conducteurs
disponiblespourlamédecinenucléaire,leursavantagesetleurslimites.
Lesgamma-camérasd’Angersontbaséessurleprincipedeconversionindirecte:
lephotongamma incidentest converti enphotons lumineuxpuisen signal électrique.
Cette méthode utilise un cristal scintillant d’iodure de sodium (NaI) et des tubes
photomultiplicateurs.
Les gamma-caméras à semi-conducteurs (Figure 1 Principes de conversion
indirecteetdirecte)sontbaséessurleprincipedeconversiondirecteduphotongamma
(g)incidentenpaires«électron–trou»(signalélectrique)proportionnelàsonénergie.
Sous l’action d’un champ électrique appliqué entre les électrodes, les charges se
déplacent:lesélectronsversl’anodeetlestrousverslacathode.
Lesignalélectriquedesortie,récupérésurchaqueélectrode,possèdealorsune
amplitudeproportionnelleàl’énergieduphotongammaincident.
7
Figure1Principesdeconversionindirecteetdirecte
Conversionindirecte(NaI)àgauche,etconversiondirecte(CZT)(56)àdroite.
Laconversiondirected’unphotongammadansunmatériausemi-conducteursans
étapeintermédiaireprésenteschématiquementtroisavantages(42):
- (i)Améliorationdelasensibilitédedétection:contrairementauprincipede
conversion indirecte des gamma-caméras conventionnelles (conversion du
photon gamma incident en photons lumineux puis en signal électrique),
l’interactiond’unphotongammad’énergie140kilo-électron-volts(keV)dansun
matériauCZTproduit environ30000paires électron-trou, soit environ20 fois
plusqu’avecuncristalscintillantdeNaI(57).
- (ii)Améliorationde la résolution spatiale : les charges créées à l’endroit de
l’interaction sont entraînées sous l’action d’un champ électrique en conservant
l’informationspatiale.Lematériausemi-conducteurpeutdoncavoiruneépaisseur
importantesansdégraderlarésolutionspatiale.
- (iii)Améliorationdelarésolutionenénergied’unfacteurdeuxparrapportau
détecteurNaIpourdesphotonsgammad’énergie140keV(5%versus10%)(1,2)
permettantunemeilleurediscriminationdel'énergiedesphotons(99mTcet123I)
enimageriedouble-isotope.Lesignalétantdirectementexploitableparlescircuits
électroniques,ilyauneréductiondubruitliéautraitementdusignal.
8
Le détecteur semi-conducteur idéal enmédecine nucléaire devrait posséder les
caractéristiquesphysiquessuivantes:
– Unbonpouvoird’arrêtetdedétectiondesphotonsgammaincidents,permispar
uncoefficientd’absorption,unnuméroatomiqueetunedensitéélevés,
– Un fonctionnement à température ambiante, permis par une grande résistivité
pourquelebruitdûauxfluctuationsducourantd’obscuritésoitfaible,
– Une bonne sensibilité et une résolution en énergie améliorée par une bande
interditedefaiblelargeurpourunebonnecollectedecharges,
– Uneénergied’ionisationfaiblepourquelenombredepairesélectron-troucréées
parphotongammaincidentsoitleplusélevépossible,
– Un cristal de bonne qualité pour limiter la collection imparfaite de charges,
responsable d’un effet de trainée (« tailing effect ») vers les basses énergies
(Figure2SpectresénergétiquessurlaDNM530c).
Figure2SpectresénergétiquessurlaDNM530c
0
5
10
15
20
25
30 50 70 90 110 130 150 170 190
No
rmal
ised
co
un
ts
Energy (keV)
123I 99mTc 123Iand99mTc
123I and 99mTc99mTcI
0
20
40
60
80
100
30 80 130 180
Coups n
orm
alis
és
Energie (keV)
99mTc123I 123I and 99mTc
9
Les spectres énergétiquesobtenuspar sourcesponctuelles (absencedediffusé)de1,7mégabecquerels
(MBq)de99mTc,d’123Ipuisendoubleisotope(99mTcet123I)montrentdeuxpicsénergétiquesdistinctset
l’effetdetraînée(58)verslesbassesénergies
Lesprincipauxsemi-conducteursutiliséspourladétectiondephotonsgammasontle
germanium(Ge),lafamilledestellururesdecadmium(CdTeetCdZnTe),lesilicium(Si)
etl’ioduredemercure(HgI2).
Le matériau semi-conducteur utilisé dans les applications médicales pour cette
nouvelle génération de gamma-caméras est le tellurure de cadmium-zinc (CZT). Il
présente les meilleurs compromis (59). Le CZT fonctionne à température ambiante,
possède une meilleure sensibilité sans perte de résolution, un rapport signal/bruit
nettementsupérieuràceluidesdétecteursconventionnelsutilisantuncristalscintillant.
Sonnuméroatomiqueetsadensitésontélevés,assurantunebonneefficacitédedétection
desphotonsgammaavecunefaibleépaisseur.Lepouvoird’arrêtde5mmdeCZTetde9
mmdeNaI(gamma-caméraconventionnelle)estrespectivementde80%vs100%pour
desphotonsd’énergie140keV(99mTc)etde78%vs84%pourdesphotonsde159keV
(123I).
Sespropriétésdetransportdechargessontbonnespuisquelamobilitéetladuréede
viedeschargespermettentl’obtentiond’unerésolutionenénergiedel’ordrede5%à
140keV(Figure2SpectresénergétiquessurlaDNM530c)vs9%pourlesgamma-caméras
conventionnelles.Lesméthodesdeproductiondecematériausontoptimiséeset ilest
désormaisdisponiblesurlemarché.Lesdétecteursàsemi-conducteursCZTprésentent
cependantdeslimites:
– (i) La faible épaisseur du détecteur (5 mm (60)) est responsable d’une faible
efficacité de détection des photons gamma d’énergie élevée (actuellement,
l’acquisitionen131I,dontlepicd’énergieestde364keV,n’estpaspossible),
– (ii)LesnombreuxdéfautsdumatériauCZTsontresponsablesd’uneffetdetraînée
vers les basses énergies (et d’un élargissement du spectre énergétique) : la
collection imparfaite de charge par piégeage des trous entraîne une sous-
estimationdel’énergiedesphotonsdétectés(Figure2Spectresénergétiquessurla
DNM530c).Ilexisteainsiunnombreimportantdephotonsnon-diffusés(photons
primaires)détectésavecuneénergieréduite.Lasegmentationenpetitspixelsdu
10
détecteur CZT est responsable d’un effet de diffusé inter-cristal et participe
égalementàl’effetdetrainée(61).
– (iii)Fragile,soncoûtdefabricationetderevientplusimportantquelecristalà
scintillationlimitelasurfaceetl’épaisseurdudétecteurCZT.
Lesdeuxgamma-camérasayantpermiscetravail(laDNM530cetlaDSPECT)utilisent
lemêmesemi-conducteursCZT,produitparlemêmeindustriel:laDNM530cutilise76
détecteurs(19x4)alorsquelaDSPECTenutilise36(9×4).
B. LaDNM530c
LaDNM530cutilise19détecteursàsemi-conducteursCZT(1,56,62).L’acquisition
eststationnaire,entroisdimensions,sur180°.Chacundes19détecteursestéquipéd’un
collimateur sténopé, immobile et convergent vers un ellipsoïde (axes de 18 x 16 cm)
(Figure3ImageetschémadelacaméraDNM530c).Lasynchronisationàl’ECGencours
d’acquisition permet une acquisition stationnaire en quatre dimensions (Le volume
d’acquisitiontridimensionnelleetl’informationdelasynchronisationcardiaque).
Figure3ImageetschémadelacaméraDNM530c
Statif identique à celui d’une gamma-caméra conventionnelle (56) (à gauche) et représentationschématiquedumodededétection(63)(àdroite).
La résolution spatiale intrinsèque élevée (taille des voxels de 4 mm) permet
d’avoir de petits détecteurs tout en maintenant une bonne sensibilité. Chacun des
11
détecteursCZTmesure8x8cmetsecomposedequatremodulesde40×40x5mm,
d’unematricede32×32pixels,dedimension2,46×2,46mm(56,62).Uneacquisition
tridimensionnelle stationnaire avec synchronisation à l’ECG permet l’obtention d’une
sensibilitédedétectionetdeséchantillonnagesangulairessuffisants.L’examendupatient
peutêtreeffectuéendécubitusventraloudorsal.
LesdétecteursCZT sontdisposés en trois rangées avec les rangées extérieures
contenantmoinsdedétecteursquelarangéedumilieu,soit19détecteursautotal(Figure
4 Configuration des détecteurs CZT de la DNM 530c). La collimation sténopée de ces
détecteursconvergeverslemêmepointfocal.Levolumed’acquisitionestunellipsoïde
d’environ18× 16 cm. La sensibilité varie dans ce volume en raisonde la collimation
sténopée(1).Cettesensibilitévariableconduitàuneréductiondutauxdecomptagedes
photonsémisparlesorganesvoisins,ceux-ciétantsituésplusloindupointfocal(64).Cet
effetestcompenséparl’acquisitionsimultanéedes19projections.
Figure4ConfigurationdesdétecteursCZTdelaDNM530c
(A) Collimation multi-sténopée (19) couvrant le volume cardiaque. (B) Collimation sténopée etminiaturisationdudétecteurCZTpixélisé permettant une acquisitionprochedu cœur, dont l’image estréduite.(C)Photomultiplicateurclassiqued’unegamma-caméraconventionnellecomparéàundétecteurCZT(40×40x5mm).(D)BoîtededétecteursCZTavecsesconnexionsélectroniques.(E)DétecteursCZTpixélisés avec résolution spatiale intrinsèque d’environ 2,5 mm quelle que soit l’énergie des photonsincidents(1).
Cette configuration est responsable d’une inhomogénéité du champ
d’acquisition et d’un artéfact de troncature, non présents sur les gamma-caméras
conventionnelles,àcollimationparallèle(65).
12
Chaque pixel CZT a sa propre unité de traitement électronique, réduisant
considérablementletempsmortàdestauxdecomptageélevés(66).
LareconstructiondesimagestomographiquesesteffectuéesurunestationXeleris
(General ElectricHealthcare,Milwaukee,Wisconsin) par un logiciel de reconstruction
propriétaire. Cet algorithme de reconstruction prend en compte la géométrie
d’acquisition des collimateurs sténopés (Figure 5 Spectre énergétique d’une source
ponctuelle d’123I), sans correction d’atténuation, des effets de diffusé (scatter), de
contaminationcroisée(crosstalk)oudetrainéeverslesbassesénergies(tailingeffect)
(Tableau1ComparaisondelaDNM530cetdelaDSPECT).
Figure5Spectreénergétiqued’unesourceponctuelled’123I
Sourcede1,5MBq:acquisitionparles19collimateurssténopés(enhaut)etspectreénergétiqueaveceffetdetrainéeverslesbassesénergies(enbas)
Les détails complets de la procédure de reconstruction sont protégés par des
droits et restrictions commerciales. La reconstruction est réalisée avec une méthode
itérativestatistiquedetypeMLEM(maximumlikelihoodexpectationmaximization)(67)
adaptée avec une correction de type Green’s One-Step-Late (OSL) (55,68). Le voxel
reconstruitestisotropique(4x4x4mmvs4,92x4,92x4,92mmvssurlaDSPECT).
13
C. LaDSPECT
LacaméraDSPECTutiliselesmêmesdétecteursàsemi-conducteursCZTpixélisés
que ceux de la DNM 530c, mais la géométrie du système d’acquisition est différente
(Tableau1ComparaisondelaDNM530cetdelaDSPECT).
Le système est composé de 9 colonnes de détectrices mobiles. Chacune est
constituéed’unematricedepixelsCZT,comportant1024pixels(64pixelsenhauteuret
16pixelsenlargeur).Chaquepixelmesure2,46x2,46mmetsonépaisseurestde5mm
(2).Unecollimationparallèleentungstène(vsconvergentefocaliséesurlecœurpourla
DNM 530c), de taille identique à lamatrice de cristaux CZT, est disposée sur chaque
détecteur.Lestrousdececollimateurparallèlesontalignésenfacedechaquepixeldu
détecteurCZTetl’épaisseurdesseptaestde0,2mm.Chaquephotonγquiinteragitdans
un pixel CZT bénéficie d’une détection directe et d’une localisation automatique. Les
colonnesdedétecteurssontmotorisées,réalisantdesmouvementsderotationautourde
leuraxecentralpendant l’acquisitionexplorant120projectionssur levolumeexploré.
Pendantl’examen,lepatientestenpositiondedécubitusdorsaloupeutêtreinstalléen
positionsemi-assise(Figure6CaméraDSPECT).
Figure6CaméraDSPECT
CaméraDSPECT,équipéed’unsystèmedeneufdétecteursmobiles(2).
L’acquisitionsedérouleendeuxétapes:
- une«pré-acquisitioncourte» (appelée«pre-scan»)durant20à30 secondes.
Cettepremièrepartiepermetàl’opérateurdedéfinirunerégiond’intérêt(ROI)
centréesurlecœur.
14
- ladeuxièmepartieest l’acquisition tomoscintigraphiqueproprementdite.Cette
acquisitionestobtenuepardeuxsériesde60projectionspardétecteur.Entreces
2séries,les9colonnesdedétectioneffectuentunmouvementdetranslationafin
de couvrir l’ensemble du volume à étudier. Au niveau du volume de l’aire
cardiaquedéfinieparlaROIdel’étapeprécédente,un«sur-échantillonnage»est
réaliséendiminuantlesanglesdeprojection(augmentationdelastatistiquede
comptagedanscetteROI)(69)
Nostravauxontutilisélesméthodesdereconstructionsproposéesenroutineparles
constructeurs.L’algorithmedereconstructionest«propriétaire»,basésuruneméthode
itérative OSEM 3D (pour « Ordered Subsets Expectation Maximization ») (70) qui
correspondàuneméthodeMLEMaccéléréeparletridesprojectionsensous-ensembles,
avec32sous-ensemblesetunnombred’itérationschoisiparl’opérateur.Cetalgorithme,
appeléBroadview®,estdéveloppéspécifiquementpourlacaméraDSPECT.Ilintègrela
géométrie de détection du système permettant une compensation de la perte de
résolutionspatialeaveclaprofondeur.Ilintègreunecorrectiondeseffetsdediffusé,de
contamination croisée, et de trainée vers les basses énergies uniquement lors des
acquisitions double-isotope (et non simple-isotope), selon laméthode Kacperski et al
(71).Iln’yapasdecorrectiond’atténuation(2).Levoxelreconstruitestisotropique(4,92
x4,92x4,92mmvs4x4x4mmsurlaDNM530c).
Tableau1ComparaisondelaDNM530cetdelaDSPECT
DNM530c DSPECTNombrededétecteursCZT 19x4(76) 9x4(36)Compositiond’undétecteurCZT
modules(40x40x5mm)pourunematricede32x32pixelsdedimension2,46x2,46mm
Géométried’acquisitioncollimationmulti-sténopée,statique,convergente
collimationparallèle,mobile
Sensibilité x4 x7Résolutionenénergie 4à5%Résolutionspatiale(mm) 6,7 8,6Tailleduvoxelreconstruit 4x4x4mm 4,92x4,92x4,92mmCorrectiondeseffetsdediffusé,contaminationcroisée,etdetrainéeverslesbassesénergies(post-traitement)
absencedecorrectioncorrectionenacquisition
double-isotope
Inhomogénéitéduchampd’acquisition
oui non
Artefactdetroncature oui non
15
D. Acquisitionsendouble-isotope
1. Principes
Lafaisabilitéd’imageriemulti-isotopesimultanéesembleunavantageprometteur
des acquisitions TEMP. Cette imagerie permettrait d’obtenir des études multi-
fonctionnellessanserreurdelocalisationoudedifférencedetemps.(72).
Malgréunemeilleurerésolutionenénergie,lafractiondediffuséresteélevéeavec
les gammas-caméras à semi-conducteur (30% vs 34% avec les gamma-caméras
conventionnelles)(2).Deplus,l’effetdetrainéeverslesbassesénergiesobservédansle
spectre énergétique, en raison d’une collection imparfaite de charge (58) affecterait
particulièrementlastatistiquedecomptagedescamérasCZT.
Cesdeuxphénomènesimpacteraientl’acquisitiondesimagesauseinduphotopic
du99mTclorsd’uneacquisitiondouble-isotope99mTc/123I,compromettantl’exactitudede
l’étude99mTc.
2. Artefactsdel’acquisitiondouble-isotope
a) Artéfactsdel’imageriedouble-isotope
L’unedesparticularitésdesacquisitionsscintigraphiquesestdepouvoirétudier
simultanémentdeuxfonctionsd’unmêmeorgane.Leprincipaldéfipourlesacquisitions
endouble-isotopesimultanéesestlacorrectiondeseffetsdudiffusé(«scatter»)etdela
contaminationcroisée(«crosstalk»)entrelesisotopespossédantuneénergiedifférente
d’émission gamma, responsables d’un contraste d’image dégradé et d’une étude
quantitativealtérée.Denombreusesméthodesdecorrectionsdeseffetsdudiffuséetde
la contamination croisée ont été proposées pour les acquisitions en double-isotope.
Citonsparexemplelafenêtred’énergieasymétriqueduphotopicdel’123I(73),quiréduit
l’efficacitédu comptage en comparaison àune fenêtred’énergie symétrique (74).Une
autreméthodedecorrectionestlaméthodedecorrectionendoublefenêtrageoutriple
fenêtrage(tripleenergywindow;TEW)(75)(Figure7Fenêtresénergétiquesd'acquisition
entriplefenêtrage(TEW)).
16
Figure7Fenêtresénergétiquesd'acquisitionentriplefenêtrage(TEW)
Pourchaquephotopic,unefenêtreprincipaleetdeuxsous-fenêtressontpositionnées.Cl,Cm,etCrindiquentrespectivement le nombre de coups de la fenêtre gauche, centrale et droite. Wl, Wm, et Wr indiquentrespectivementlalargeurdelafenêtredegauche,centrale,etdroite(75).
De nombreuses autres méthodes de correction des effets du diffusé et de la
contaminationcroiséeontétédéveloppéespourreconstruirelesacquisitionsendouble-
isotopedesgamma-camérasconventionnelles,notammentcérébrales(76-80).D’autres
modélisationsdecorrectiondeseffetsdudiffuséetdelacontaminationcroiséeétaient
basées sur l’estimation de diffusé de la source (Effective Source Scatter Estimation ;
ESSE)(81),ladétectionforcéedeconvolution(ConvolutionForcedDetection;CFD)basée
surlessimulationsrapidesMonte-Carlo(77).Cesmodélisationsontétésouventutilisées
etontprouvéleurprécisiondansl’estimationdudiffusé.
b) Particularitésdudiffuséetdelacontaminationcroiséedansles
gammas-camérasCZT:
Malgréuneaugmentationde lasensibilitéetde larésolutionenénergie, lapartde
diffusé dans les caméras CZT reste élevée, supérieure à 30%, versus 34% pour les
camérasconventionnelles(2).Lesméthodesdecorrectiondelacontaminationcroiséeet
dudiffuséenimageriedouble-isotopesontpluscompliquéespourlesraisonssuivantes:
17
– (i) La collection de charges imparfaite et le diffusé inter-cristal (82) sont
responsablesd’uneffetdetraînée(«tailingeffect»)verslesbassesénergiesdans
le spectre énergétique des gamma-caméras CZT,même en l’absence de diffusé
intra-objet(Figure2SpectresénergétiquessurlaDNM530c).Ceteffetdetraînée
est responsable d’une contamination croisée additionnelle entre les différents
isotopes.Lediffuséseraitsurestimésilaméthodedetriplefenêtragedecorrection
dudiffuséétaitutilisée(83).
– (ii)Cesgamma-camérasdédiéesauxexplorationscardiaquespossèdentunpetit
volume d’acquisition et l’activité hors de ce volume d’acquisition ne peut être
correctementreconstruite.Ainsi,lesmodèlesdecorrectiondesgamma-caméras
conventionnelles(parexempleEffectiveSourceScatterEstimation,ESSE(81))ne
peuventêtreappliquéssurcettegamma-caméracarilsnécessitentdeconnaître
précisémentladistributiondel’activitédansl’objetentier.
Récemment,Fanetal(84)pourlaDNM530cetHolstenssonetal(84)pourlaDSPECT
ontdéveloppéunmodèle sophistiquédecorrectionadaptéà lagéométriedusystème
d’acquisition de chaque gamma-caméra CZT. Lors d’acquisition simultanée double-
isotope(123Iet99mTc),cesalgorithmesdecorrectioncorrigedeseffetsdediffuséetdela
contamination croisée, et extrait les photons primaires utiles du 99mTc et de l’123I des
donnéesdeprojection,en tenantcomptede l’effetde trainéevers lesbassesénergies.
Leursapprochesontpermisunebonneprécisiondecorrectionetsemblentprometteuses.
Cependant,enraisondel'algorithmedereconstructionrequis(MLEM),etdesparamètres
àoptimiser(72),cesdeuxméthodesdereconstruction(84)récentesetprometteusesne
sontpasinstalléesparlesconstruteurssurleursconsolesenconditionderoutine.
Danscetravail,toutelesreconstructionsontétéeffectuéesenutilisantlesconsoles
des constructeurs et les logiciels disponibles pour les deux caméras. En routine, les
méthodesdecorrectiondudiffusé,delacontaminationcroiséeetdel’effetdetrainée(84)
nesontpasinstalléesparGEpourlaDNM530c.
LesacquisitionseffectuéessurlaDSPECTontétécorrigées,lorsd’acquisitiondouble-
isotope,dudiffusé,delacontaminationcroiséeetdel’effetdetrainéeselonlaméthodede
Kacperskietal.(71),installéeenroutinesurlesstationsdepost-traitementdelaDSPECT,
maisnond’Holstenssonetal.(84).
18
III. :Etudesurfantômedynamiquedelafonction
ventriculairegauche(99mTc)enprésenced’123I
A. Résumé
Contexte : L’apportde l’améliorationde la résolutionenénergiedes camérasà semi-
conducteur CZT sur l'évaluation de la fonction ventriculaire gauche en conditions
d’acquisitionsdouble-isotope(99mTcet123I)resteinconnu.
Le fantôme cardiaque dynamique-Amsterdam (AGATE, Vanderwilt techniques, Boxtel,
Pays-Bas)aété rempli successivementd'unesolutiond’123I seul,de 99mTcseuletd’un
mélanged’123Ietde99mTc.Autotal,12jeuxdedonnéesontétéacquisavecchaquecaméra
CZTdisponibledanslecommerce(DNM530cetDSPECT)enutilisantlesdeuxfenêtres
d'énergie(99mTcou123I)etunefractiond'éjectionrégléeà33,45puis60%.Lesvolumes
ventriculaires (VTDetVTS), laFEVG, lemouvementrégionalde laparoi (modèleà17
segments)ontétéévaluésàl'aidedulogicielQGS(Cedars-Sinaï).Laconcordanceentreles
acquisitionssimple-etdouble-isotopeaététestéeàl'aideducoefficientdecorrélationde
concordancedeLin(CCC)etdesdiagrammesdeBland-Altman.
Résultats : Il n'y avait pas de différence significative entre l'acquisition simultanée
double-isotope(123Iet99mTc)pourleVTD,leVTS,laFEVG,oulemouvementsegmentaire
de la paroi. Les volumes myocardiques en simple- (123I, 99mTc) et double-isotope
(reconstruitsaveclesdeuxfenêtresd’énergie123Iet99mTc)ontétérespectivement:VTD
(mL)88±27vs89±27vs92±29vs90±26pourlaDNM530c(p=NS)et82±20vs83
±22vs79±19vs77±20pourlaDSPECT(p=NS);VTS(mL)40±1vs41±2vs41±2
vs42±1pourlaDNM530c(p=NS)et37±5vs37±1vs35±3vs34±2pourlaDSPECT
(p=NS);FEVG(%)52±14vs51±13vs53±13vs51±13pourlaDNM530c(p=NS)et
52±16vs54±13vs54±14vs54±13pourlaDSPECT(p=NS);mouvementrégional
(mm)6,72±2,82vs6,58±2,52vs6,86±2,99vs6,59±2,76pourlaDNM530c(p=NS)
et6,79±3,17vs6,81±2,75vs6,71±2,50vs6,62±2,74pourlaDSPECT(p=NS).Letype
decaméran'aeuqu’unimpactsignificatifsurleVTS(p<0,001).
Conclusions : Les nouvelles caméras CZT ont donné des résultats similaires pour
l'évaluationdelaFEVGetlemouvementrégionaldanslesdifférentesfenêtresd'énergie
(123I ou 99mTc) et les types d'acquisition (simple- vs double-isotope). Avec les deux
camérasCZT, laprésenced’123In'apaseud'impactsurl'évaluationdelaFEVGdansla
fenêtred'énergiedu99mTcenacquisitionssimultanéesdouble-isotope.
19
Communicationsorales:
*EANM2013,Lyon*EANM2015,Hamburg
Publication:publiéeparl’EJNMMIPhysics2016,dec
20
ORIGINAL RESEARCH Open Access
Left ventricular function assessment using123I/99mTc dual-isotope acquisition with twosemi-conductor cadmium–zinc–telluride(CZT) cameras: a gated cardiac phantomstudyTanguy Blaire1,2,3*, Alban Bailliez1,2,3, Fayçal Ben Bouallegue4, Dimitri Bellevre4, Denis Agostini2,4
and Alain Manrique2,4
* Correspondence:
[email protected] Medicine, UF 5881,
Groupement des Hôpitaux de
l’Institut Catholique de Lille,
Lomme, France2Normandie Univ, UNICAEN,
Signalisation, électrophysiologie et
imagerie des lésions
d’ischémie-reperfusion
myocardique, 14000 Caen, France
Full list of author information is
available at the end of the article
Abstract
Background: The impact of increased energy resolution of cadmium–zinc–telluride
(CZT) cameras on the assessment of left ventricular function under dual-isotope
conditions (99mTc and 123I) remains unknown.
The Amsterdam-gated dynamic cardiac phantom (AGATE, Vanderwilt techniques,
Boxtel, The Netherlands) was successively filled with a solution of 123I alone, 99mTc
alone, and a mixture of 123I and 99mTc. A total of 12 datasets was acquired with each
commercially available CZT camera (DNM 530c, GE Healthcare and DSPECT,
Biosensors International) using both energy windows (99mTc or 123I) with ejection
fraction set to 33, 45, and 60 %. End-diastolic (EDV) and end-systolic (ESV) volumes,
ejection fraction (LVEF), and regional wall motion and thickening (17-segment
model) were assessed using Cedars-Sinai QGS Software. Concordance between single-
and dual-isotope acquisitions was tested using Lin’s concordance correlation coefficient
(CCC) and Bland–Altman plots.
Results: There was no significant difference between single- or simultaneous
dual-isotope acquisition (123I and 99mTc) for EDV, ESV, LVEF, or segmental wall
motion and thickening. Myocardial volumes using single- (123I, 99mTc) and dual-isotope
(reconstructed using both 123I and 99mTc energy windows) acquisitions were,
respectively, the following: EDV (mL) 88 ± 27 vs. 89 ± 27 vs. 92 ± 29 vs. 90 ± 26
for DNM 530c (p = NS) and 82 ± 20 vs. 83 ± 22 vs. 79 ± 19 vs. 77 ± 20 for DSPECT
(p = NS); ESV (mL) 40 ± 1 vs. 41 ± 2 vs. 41 ± 2 vs. 42 ± 1 for DNM 530c (p = NS)
and 37 ± 5 vs. 37 ± 1 vs. 35 ± 3 vs. 34 ± 2 for DSPECT (p = NS); LVEF (%) 52 ± 14
vs. 51 ± 13 vs. 53 ± 13 vs. 51 ± 13 for DNM 530c (p = NS) and 52 ± 16 vs. 54 ± 13
vs. 54 ± 14 vs. 54 ± 13 for DSPECT (p = NS); regional motion (mm) 6.72 ± 2.82 vs.
6.58 ± 2.52 vs. 6.86 ± 2.99 vs. 6.59 ± 2.76 for DNM 530c (p = NS) and 6.79 ± 3.17 vs.
6.81 ± 2.75 vs. 6.71 ± 2.50 vs. 6.62 ± 2.74 for DSPECT (p = NS). The type of camera
significantly impacted only on ESV (p < 0.001).
(Continued on next page)
EJNMMI Physics
© The Author(s). 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 InternationalLicense (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium,provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, andindicate if changes were made.
Blaire et al. EJNMMI Physics (2016) 3:27
DOI 10.1186/s40658-016-0163-2
B. Publicationcorrespondante(EJNMMIPhysics,2016)
21
Methods
Gated phantom studies
We used the Amsterdam gated (Agate) dynamic phantom (Vanderwilt techniques,
Boxtel, The Netherlands) as a reference for volume and LVEF measurements [15]. This
phantom is a realistic 3-D water-filled torso with two thin membranes simulating endo-
cardial and epicardial walls with known ejection fraction (Fig. 2). The compartment
between these membranes was successively filled with a solution of 123I alone, 99mTc
alone, and a mixture of 123I and 99mTc (22/44 kBq/mL, respectively) simulating the
myocardial wall. The cardiac phantom stroke volume was controlled by a
programmable adjustable pumping system, and an ECG-triggered signal was produced
at a constant heart rate. Four datasets (single 123I, single 99mTc, dual 123I, and 99mTc)
were acquired using three different ejection fractions (33 and 45 % to mimic LV dys-
function and 60 % to simulate normal LV function) on each camera (DNM 530c and
DSPECT) with the following parameters: 10-min acquisition and 70-bpm contraction
Fig. 1 Energy spectra using DNM 530c. Typical single 123I, single 99mTc, and simultaneous (123I and 99mTc)
point source (1.7 MBq) energy spectra using DNM 530c without in-object scatter. Notice the low tailing
effect and the down-scatter of 123I towards 99mTc in the dual isotope condition
Fig. 2 The AGATE dynamic gated phantom. The AGATE dynamic gated phantom with fillable cardiac set,
successively filled with a solution of 123I alone, 99mTc alone, and a mixture of 123I and 99mTc
Blaire et al. EJNMMI Physics (2016) 3:27 Page 3 of 11
22
rate. EDV, ESV, LVEF, and regional wall thickening and motion (17-segment model)
were assessed using Quantitative Gated SPECT software (QGS, Cedars-Sinai Medical
Center, Los Angeles, CA). The acquisition parameters were as follows: 70 × 70 matrix
for the DNM 530c system and 64 × 64 for the DSPECT with a total of 120 projections
recorded by each block in the heart area defined on a short prescan acquisition [13].
The energy window was asymmetric for both cameras, 140 keV (−10 + 5 %) for 99mTc
and 159 keV (−5 + 10 %) for 123I, for each acquisition.
CZT cameras
We successively used (i) a DNM 530c equipped with a multiple pinhole collimator and
19 stationary CZT detectors that simultaneously image 19 cardiac views, each detector
being composed of four 5-mm-thick elements of 32 × 32 pixels (pixel size 2.46 ×
2.46 mm) [16] and (ii) a DSPECT operating with nine mobile blocks of pixelated CZT
detectors (pixel size 2.46 × 2.46 mm) associated with a wide-angle square-hole tungsten
collimator, recording a total of 120 projections by each block [13]. All SPECT data were
acquired and reconstructed using the parameters currently recommended for clinical
routine and provided by each manufacturer, leading to a reconstructed pixel size of
4 × 4 × 4 and 4.92 × 4.92 × 4.92 mm for DNM 530c and DSPECT, respectively. No
attenuation correction was performed.
Statistical analysis
Values are presented as mean ± SD. A linear model analysis evaluated the effect of
camera, acquisition type (single- vs. dual-isotope), isotope (123I vs. 99mTc), and the
interaction between camera type and isotope. Continuous mean values were compared
using the Wilcoxon signed-rank test or Mann–Whitney U test when appropriate.
Relationship between DNM 530c and DSPECT results were assessed using Pearson’s
(r) correlation coefficient, Bland–Altman limit-of-agreement, and Lin’s concordance
correlation coefficient (CCC), a measure of both precision and bias [17, 18]. Lin’s CCC
measures the equivalence of two measurement methods. The accuracy (i.e. the
deviation of the best fit line from the line of identity) was assessed using the bias cor-
rection factor calculated as C.b = CCC/r, r being Pearson’s correlation coefficient. The
values of r and CCC were characterised using the Landis and Koch scale (0.2–0.4: fair;
0.4–0.6: moderate; 0.6–0.8: substantial; 0.8–1.0: almost perfect) [19]. A p value <0.05
was considered statistically significant.
Statistical analyses were performed using R software (R Foundation for Statistical
Computing, version 3.2.4, Vienna, Austria) except the linear model analysis performed
using JMP 11 (SAS institute, Cary, NC).
Results
The mean values of overall cardiac volumes (EDV and ESV), LVEF, and regional wall
motion and thickening using single- and dual-isotope acquisitions with DNM 530c and
DSPECT are shown in Table 1 and illustrated in Figs. 3 and 4.
Linear model analysis demonstrated that the type of camera but not the acquisition
mode (i.e. single- or dual-isotope) impacted on volume measurements. Post hoc
Mann–Whitney test showed that this impact was only observed for the ESV
Blaire et al. EJNMMI Physics (2016) 3:27 Page 4 of 11
23
measurements (p < 0.0001) whereas EDV, LVEF, and segmental wall motion were
similar for the two cameras.
Lin’s concordance correlation coefficient and Bland–Altman plots (see Tables 2 and 3
and Fig. 5) revealed an almost perfect agreement between single- and dual-isotope
acquisitions for assessing segmental wall motion and thickening with 99mTc with both
CZT cameras. Conversely, using 123I, the agreement was weaker with both CZT
cameras, with a decreased CCC and an increased 95 % CI of the difference between the
two measurements on Bland–Altman plots. Pearson’s correlation (r) and CCC were
similar, also indicating that no systematic bias was present (C.b > 0.97) between the two
cameras and the acquisition mode.
Discussion
Our results demonstrated the feasibility of LVEF evaluation using gated perfusion
SPECT with CZT cameras. On simultaneous dual radionuclide acquisitions, the 99mTc
photopeak was unaffected by 123I scatter and crosstalk. To our knowledge, this is the
first dual-isotope gated phantom study evaluating ventricular function using the two
commercially available CZT cameras (DNM 530c and DSPECT).
Table 1 Results for each camera
Camera DNM 530c DSPECT
Energywindow
123I 99mTc 123I 99mTc
Acquisitiontype
Single Dual Single Dual Single Dual Single Dual
EDV (mL) 88 ± 27 92 ± 29 89 ± 27 90 ± 26 82 ± 20 79 ± 19 83 ± 22 77 ± 20
ESV (mL) 40 ± 1* 41 ± 2* 41 ± 2* 42 ± 1* 37 ± 5 35 ± 3 37 ± 1 34 ± 2
LVEF (%) 52 ± 14 53 ± 13 51 ± 13 51 ± 13 52 ± 16 54 ± 14 54 ± 13 54 ± 13
Motion (mm) 6.72 ± 2.82 6.86 ± 2.99 6.58 ± 2.52 6.59 ± 2.76 6.79 ± 3.17 6.71 ± 2.50 6.81 ± 2.75 6.62 ± 2.74
Thickening(%)
47.7 ± 30.6 47.1 ± 29.9 45.4 ± 27.7 44.3 ± 29.2 44.2 ± 28.8 42.7 ± 23.6 42.2 ± 24.5 41.5 ± 26.7
Phantom study results for each camera model expressed as mean ± SD. EDV, ESV, LVEF, and thickening and motion mean
values for 99mTc and 123I isotope in two acquisition types (single or dual), for both energy windows (123I and 99mTc) on
each camera (DNM 530c and DSPECT). *p < 0.0001 vs. DSPECT
Fig. 3 DNM 530c and DSPECT 99mTc and 123I uptake. Single 123I (a) and single 99mTc (b). Simultaneous 123I
(c) and 99mTc (d) end-systolic apical short axis uptake for DNM 530c (upper row) and DSPECT (lower row) for
LVEF 50%
Blaire et al. EJNMMI Physics (2016) 3:27 Page 5 of 11
24
Dual-isotope acquisition with CZT cameras remains a challenging technique.
Impaired myocardial innervation leads to low myocardial 123I-mIBG uptake, requiring
a dual-isotope protocol to localise the heart [12]. Due to the small field-of-view of the
dedicated CZT cardiac cameras, a scout view is mandatory to localise the heart and
correctly centre the field-of-view prior to SPECT acquisition. In addition, most of the
patients referred for 123I-mIBG assessment have an ischemic cardiomyopathy with
heart failure (66 % in the ADMIRE-HF study [20]). In this clinical setting, the dual-
isotope protocol allows a simple and efficient co-registration of innervation and perfu-
sion studies and thus a robust assessment of innervation-perfusion mismatch. The
measurement of LV function is a key step of prognosis assessment and may potentially
be altered when using CZT cameras with a simultaneous dual-isotope protocol due to
the down-scatter, crosstalk, and tailing effect of 123I in the 99mTc photopeak.
Fig. 4 DNM 530c and DSPECT end-systolic volume rendering, volume (mL), and filling (mL/s). End-systolic
volume rendering, volume (mL), and filling (mL/s) in single 99mTc (a) and dual 99mTc (b) condition using
DNM 530c (upper row) and DSPECT (lower row)
Table 2 DNM 530c and DSPECT concordance correlation coefficients for motion
Motion Pearson’s Bland Altman
r [95 % CI] CCC [95 % CI] C.b Mean diff. [95 % CI] Regression R2
Acquisition Isotope
Single 123I 0.94 [0.89–0.96] 0.93 [0.89–0.96] 0.99 0.06 [−2.15;2.28] y = 0.123x − 0.764 0.107
99mTc 0.95 [0.92–0.97] 0.94 [0.91–0.97] 0.99 0.23 [−1.48;1.94] y = 0.088x − 0.354 0.071
Dual 123I 0.90 [0.83–0.94] 0.88 [0.81–0.93] 0.98 −0.15 [−2.8;2.5] y = −0.188x + 1.13 0.144
99mTc 0.94 [0.90–0.97] 0.94 [0.9–0.97] 1 0.03 [−1.81;1.87] y = −0.007x + 0.076 0
Camera
DSPECT 123I 0.91 [0.86–0.95] 0.89 [0.83–0.93] 0.98 0.08 [−2.57;2.72] y = 0.248x − 1.599 0.271
99mTc 0.97 [0.95–0.98] 0.97 [0.95–0.98] 1 0.22 [−1.74; 2.18] y = −0.003x + 0.239 0
DNM530c
123I 0.94 [0.90–0.97] 0.94 [0.9–0.97] 1 −0.14 [−2.11;1.84] y = −0.061x + 0.276 0.031
99mTc 0.97 [0.96–0.99] 0.97 [0.95–0.98] 1 −0.01 [−1.29;1.26] y = −0.089x + 0.576 0.135
Bland–Altman mean difference (mean diff), regression, and R2
r, Pearson’s correlation (precision); CCC, Lin’s concordance correlation; C.b, r/CCC = bias factor (trueness)
Blaire et al. EJNMMI Physics (2016) 3:27 Page 6 of 11
25
Our results demonstrated that DNM 530c provided higher systolic volumes com-
pared to the DSPECT camera. This camera effect on volume assessment is likely related
to spatial resolution. Imbert et al. [21] reported the following classification of measured
central spatial resolution: DNM 530c (6.7 mm) and DSPECT (8.6 mm). These results
are concordant with previous findings by Bailliez et al. [22] showing in both phantom
and patients that LV volumes were higher using the DNM 530c model compared to
DSPECT and to Anger camera equipped with cardiofocal collimators.
Our results also demonstrated that, in comparison with single 99mTc acquisition, dual123I/99mTc acquisition did not compromise the assessment of ventricular function using
the 99mTc photopeak. In some patients with severe heart failure, the sole use of 123I-
mIBG SPECT can lead to suboptimal localisation of the heart because of the CZT cam-
era’s narrow field-of-view, particularly when cardiac mIBG uptake is very low and the
left ventricle is dilated. A dual-isotope protocol acquisition using both perfusion and
innervation tracers provides a clear perfusion image and a perfect registration that
allows the definition of the heart contours and thus an accurate measurement of123I-mIBG uptake [12].
In the clinical setting, simultaneous dual-radionuclide acquisition provides perfectly
registered functional images leading to a reduced imaging time. In cardiac SPECT,
several dual-radionuclide imaging protocols have been proposed. Simultaneous99mTc-sestamibi/123I-BMIPP imaging was proposed for assessing rest perfusion and
fatty acid metabolism at the same time in patients with recent myocardial infarction
[23, 24]. The dual-isotope acquisition protocol using 201Tl and 123I-mIBG is well docu-
mented on conventional Anger cameras, using the triple-energy window [25] for scatter
and crosstalk correction. Simultaneous perfusion and sympathetic innervation imaging
with 123I-mIBG and 99mTc-labelled tracers enables the evaluation of innervation-flow
mismatch and may provide valuable information to target the trigger zone in the
setting of ventricular arrhythmia [4, 26]. In a recent study, Gimelli et al. [11, 27] using
sequential 123I-mIBG and 99mTc-tetrofosmin myocardial SPECT demonstrated a
relevant association between innervation derangement (123I-mIBG) and myocardial
synchronicity (99mTc-tetrofosmin).
Table 3 DNM 530c and DSPECT concordance correlation coefficients for thickening
Thickening Pearson’s Bland Altman
r [95 % CI] CCC [95 % CI] C.b Mean diff. [95 % CI] Regression R2
Acquisition Isotope
Single 123I 0.93 [0.88–0.96] 0.92 [0.86–0.95] 0.99 −3.59 [−26.45;19.28] y = −0.063x − 0.694 0.026
99mTc 0.94 [0.90–0.97] 0.93 [0.89–0.96] 0.99 −3.14 [−21.65;15.38] y = −0.125x + 2.331 0.121
Dual 123I 0.87 [0.79–0.93] 0.84 [0.75–0.9] 0.97 −4.35 [−33.78;25.08] y = −0.248x + 6.801 0.191
99mTc 0.94 [0.90–0.97] 0.94 [0.89–0.96] 1 −2.84 [−22.04;16.35] y = −0.09x + 1.009 0.067
Camera
DSPECT 123I 0.88 [0.80–0.93] 0.88 [0.81–0.93] 1 1.43 [−23.87;26.74] y = 0.208x − 7.608 0.177
99mTc 0.96 [0.93–0.98] 0.96 [0.93–0.98] 1 0.78 [−14.06;15.63] y = −0.088x + 4.449 0.09
DNM530c
123I 0.91 [0.85–0.95] 0.91 [0.85–0.95] 1 0.67 [−24.38;25.71] y = 0.026x − 0.588 0.004
99mTc 0.96 [0.94–0.98] 0.96 [0.93–0.98] 1 1.08 [−14.5;16.65] y = −0.053x + 3.446 0.037
Bland–Altman mean difference (mean diff), regression, and R2
r, Pearson’s correlation (precision); CCC, Lin’s concordance correlation; C.b, r/CCC = bias factor (trueness)
Blaire et al. EJNMMI Physics (2016) 3:27 Page 7 of 11
26
a b
c d
e f
g h
Fig. 5 Lin’s CCC and Bland–Altman motion for DNM 530c and DSPECT. Lin’s CCC for DSPECT 123I (a) and99mTc (c), DNM 530c 123I (e), and 99mTc (g) motion and Bland–Altman plots for DSPECT 123I (b) and 99mTc
(d), DNM 530c 123I (f), and 99mTc (h) motion for single and dual acquisitions
Blaire et al. EJNMMI Physics (2016) 3:27 Page 8 of 11
27
Despite a significant increase in energy resolution and sensitivity, the scatter fraction
with the CZT camera is still high, evaluated up to 30 vs. 34 % with conventional Anger
cameras [13]. Due to incomplete charge collection and intercrystal scatter, the CZT
detectors are subjected to a tailing effect below the photopeak that may lead to an
overcorrection of photon scatter when using a conventional triple-energy window
method [28]. Recently, Fan et al. for the DNM 530c [29] and Holstensson et al. for the
DSPECT [30] presented a model-based correction algorithm which extracts the useful
primary counts of 99mTc and 123I from projection data, taking into account the tailing
effect to correct the scatter and crosstalk in 99mTc–123I dual imaging. In the present
study, we did not apply any tailing effect correction and observed no significant impact
on ventricular function assessment.
All reconstructions were performed using the vendor’s workstation and available
software for both cameras. Routinely, scatter and crosstalk correction is not performed on
the DNM 530c camera. Image data from DSPECT were corrected for scatter and
crosstalk but not for the tailing effect. In our study, the ratio between 123I and 99mTc
concentration was set to 1:2, which is representative of the low 123I-mIBG myocardial
uptake, observed in severe heart failure. Under these specific conditions, the absence of
scatter and crosstalk correction using the DNM 530c did not affect ventricular function
assessment using 99mTc acquisitions. In severe heart failure, 123I-mIBG myocardial uptake
is low and we assumed that the crosstalk and scatter of 123I in the 99mTc photopeak had
no consequences.
Limitations of the study
Due to the design of the phantom, EDV and ESV were not predetermined. The
phantom was filled under static equilibrium conditions at atmospheric pressure to
provide a reproducible ejection fraction. Based on this equilibrium, ejection fraction
was imposed by injecting a stroke volume into the ventricular cavity [15, 22]. As a
consequence, true EDV and ESV were not known and thus could not be compared with
measured volumes.
As we used only commercially available software, scatter and crosstalk were corrected
with DSPECT but not with DNM 530c. However, our results displayed no critical
differences between the single-isotope and dual-isotope 99mTc window, even with the
DNM 530c. At best, the demonstration could be made by comparing the results
obtained with and without scatter and crosstalk corrections. However, the aim of our
study was to compare the results obtained with the two CZT cameras using the
dedicated commercially available software to mimic routine clinical conditions.
Conclusions
In this phantom study, the two CZT cameras (DNM 530c and DSPECT) provided
similar results for ventricular function assessment (EDV, ESV, and LVEF) with single-
(separate 123I and 99mTc acquisitions) and simultaneous dual-isotope (123I and 99mTc)
acquisitions. Further studies are needed to evaluate perfusion match and mismatch
using 123I-mIBG and 99mTc-labelled tracers.
Acknowledgements
The authors thank Nathaniel Roth for his technical assistance. This work was conducted as part of the FHU
REMOD-VHF project.
Blaire et al. EJNMMI Physics (2016) 3:27 Page 9 of 11
28
Authors’ contribution
TB and AM: design of the study, data acquisition, analysis and interpretation of data, drafting of manuscript. AB and
DB: data acquisition, analysis of data, and drafting of manuscript. FBB: statistical analysis, analysis of data and critical
revision. DA: interpretation of data, drafting of manuscript. All authors read and approved the final manuscript.
Competing interests
The authors declare that they have no competing interests.
Author details1Nuclear Medicine, UF 5881, Groupement des Hôpitaux de l’Institut Catholique de Lille, Lomme, France. 2Normandie
Univ, UNICAEN, Signalisation, électrophysiologie et imagerie des lésions d’ischémie-reperfusion myocardique, 14000
Caen, France. 3Nuclear Medicine, IRIS, Hôpital Privé Le Bois, 144 avenue de Dunkerque, 59000 Lille, France. 4Nuclear
Medicine, CHU Cote de Nacre, Caen, France.
Received: 29 June 2016 Accepted: 1 November 2016
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18. Morgan CJ, Aban I. Methods for evaluating the agreement between diagnostic tests. J Nucl Cardiol. 2016;23(3):
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20. Jacobson AF, Senior R, Cerqueira MD, Wong ND, Thomas GS, Lopez VA, et al. Myocardial iodine-123 meta-
iodobenzylguanidine imaging and cardiac events in heart failure. Results of the prospective ADMIRE-HF (AdreView
Myocardial Imaging for Risk Evaluation in Heart Failure) study. J Am Coll Cardiol. 2010;55(20):2212–21.
21. Imbert L, Poussier S, Franken PR, Songy B, Verger A, Morel O, et al. Compared performance of high-sensitivity
cameras dedicated to myocardial perfusion SPECT: a comprehensive analysis of phantom and human images. J
Nucl Med. 2012;53(12):1897–903.
22. Bailliez A, Lairez O, Merlin C, Piriou N, Legallois D, Blaire T, et al. Left ventricular function assessment using 2
different cadmium-zinc-telluride cameras compared with a gamma-camera with cardiofocal collimators: dynamic
cardiac phantom study and clinical validation. J Nucl Med. 2016;57(9):1370–5.
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23. Kumita S, Cho K, Nakajo H, Toba M, Kijima T, Mizumura S, et al. Simultaneous assessment of Tc-99m-sestamibi and
I-123-BMIPP myocardial distribution in patients with myocardial infarction: evaluation of left ventricular function
with ECG-gated myocardial SPECT. Ann Nucl Med. 2000;14(6):453–9.
24. Ouyang J, Zhu X, Trott CM, El Fakhri G. Quantitative simultaneous 99mTc/123I cardiac SPECT using MC-JOSEM.
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26. Abdulghani M, Duell J, Smith M, Chen W, Bentzen SM, Asoglu R, et al. Global and regional myocardial innervation
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27. Gimelli A, Liga R, Genovesi D, Giorgetti A, Kusch A, Marzullo P. Association between left ventricular regional
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30
IV. :Etudesurfantômeanthropomorphedetorsedela
perfusionmyocardique(99mTc)enprésenced’123I
(innervation)
A. Résumé
Contexte.Nous avons étudié et comparé l'impact de l'acquisition simultanée double-
isotopesurl'évaluationdeladiscordance123I/99mTcenutilisantdeuxcamérasCZT(la
DNM530c,etlaDSPECT).
Méthodes. Nous avons utilisé un fantôme anthropomorphe de torse (rempli
respectivementd'unesolutiond’123Iseul,de99mTcseuletd’unmélanged’123Ietde99mTc)
et son insert cardiaque équipé de deux compartiments imitant deux défauts, l’un
concordantetl’autrediscordant.L'étenduedeladiscordanceetlecontrastedel'image
reconstruiteontétéévalués.
Résultats. Le mode d'acquisition (simple- vs double-isotope) a considérablement
impacté (i) l’activitésegmentairereconstruitede99mTc(maispasd’123I)pour lesdeux
caméras (P<0,001)et (ii) le contrastede l'image (enutilisant l’123Iet laDNM530c,P
<0,0001;etenutilisantl’123Ietle99mTcaveclaDSPECT,P<0,0001).Cependant,ledéfaut
etlatailledeladiscordancen'ontpasétéaffectésparletyped'acquisition.AveclaDNM
530c et laDSPECT, le coefficient de corrélationde concordancedeLin et l'analysede
Bland-Altmanontdémontréuneconcordanceetunagrémentpresqueparfaitsentreles
activités segmentaires des acquisitions simple- et double-isotope simultanée (123I et
99mTc).
Conclusions. Cette étude n'a révélé aucun impact du mode d'acquisition (simple- vs
double-isotope)oudutypedecaméra(DSPECTvsDNM530c)surlatailledesdéfautset
la discordance en 123I et 99mTc, ce qui constitue une nouvelle étape vers l'acquisition
double-isotopesimultanéepourl'évaluationcombinéed’innervationetdeperfusion.
Publication:publiéeparleJNC2017
31
B. Publicationcorrespondante(JNuclCardiol,2017)
ORIGINAL ARTICLE
First assessment of simultaneous dual isotope(123I/99mTc) cardiac SPECT on two different CZTcameras: A phantom study
Tanguy Blaire, MD,a,b,c Alban Bailliez, MD, PhD,a,b,c Faycal Ben Bouallegue,
PhD,d Dimitri Bellevre, MD,e Denis Agostini, MD, PhD,b,e and Alain Manrique,
MD, PhDb,e
a Department of Nuclear Medicine, UF 5881, Groupement des Hopitaux de l’Institut Catholique
de Lille, Lomme, Franceb Normandie Univ, UNICAEN, Signalisation, electrophysiologie et imagerie des lesions
d’ischemie-reperfusion myocardique, FHU REMOD-VHF, Caen, Francec Department of Nuclear Medicine, IRIS, Hopital Prive Le Bois, Lille, Franced Department of Nuclear Medicine, CHU de Montpellier, Montpellier, Francee Department of Nuclear Medicine, CHU Cote de Nacre, Caen, France
Received Dec 5, 2016; accepted Feb 23, 2017
doi:10.1007/s12350-017-0841-z
Background. We studied the impact of simultaneous dual-isotope acquisition on 123I/99mTc
mismatch assessment using two CZT cameras (DNM 530c, GE Healthcare and DSPECT,
Biosensors International).
Methods. We used an anthropomorphic torso phantom (respectively filled with a solution
of 123I alone, 99mTc alone, and a mixture of 123I and 99mTc) and its cardiac insert with two
defects mimicking two matched and mismatched defects. Mismatch extent and reconstructed
image contrast were evaluated.
Results. The acquisition mode (single vs dual) significantly impacted (i) 99mTc (but not 123I)
reconstructed segmental activities using both camera (P < .001), and (ii) image contrast (using123I and DNM 530c, P < .0001; and using both 123I and 99mTc with DSPECT, P < .0001).
However, the defect and mismatch size were not impacted by the type of acquisition. With both
DNM 530c and DSPECT, Lin’s concordance correlation coefficient and Bland–Altman analysis
demonstrated an almost perfect concordance and agreement between single- and simultaneous
dual-isotope segmental activity (123I and 99mTc).
Conclusions. This study found no impact of the acquisition mode (single vs dual) or the
type of camera (DSPECT vs DNM 530c) on 123I and 99mTc defect size and mismatch, providing
a new step toward simultaneous dual-isotope acquisition for combined innervation and per-
fusion assessment. (J Nucl Cardiol 2017)
Key Words: CZT Æ DSPECT Æ DNM 530c Æ mIBG Æ dual isotope Æ mismatch
Electronic supplementary material The online version of this
article (doi:10.1007/s12350-017-0841-z) contains supplementary
material, which is available to authorized users.
The authors of this article have provided a PowerPoint file, available
for download at SpringerLink, which summarizes the contents of the
paper and is free for re-use at meetings and presentations. Search for
the article DOI on http://SpringerLink.com.
Reprint requests: Tanguy Blaire, MD, Department of Nuclear Medi-
cine, UF 5881, Groupement des Hopitaux de lInstitut Catholique de
Lille, Lomme, France; [email protected]
1071-3581/$34.00
Copyright ! 2017 American Society of Nuclear Cardiology.
Author's personal copy
32
Abbreviations123I-mIBG 123I-meta-iodobenzylguanidine
CCC Concordance correlation coefficient
CZT Cadmium-zinc-telluride
kCnts Kilo-counts
ROI Region of interest
VOI Volume of interest
BACKGROUND
The relationships between cardiac autonomic ner-
vous system dysfunction, cardiomyopathy, and cardiac
arrhythmias have been long established.1 Cardiac sym-
pathetic innervation can be directly imaged with 123I-
meta-iodobenzylguanidine (123I-mIBG), a radiolabeled
norepinephrine analog2 that reflects neuronal integrity
by visualizing reuptake and retention in cardiac sympa-
thetic terminals.3 A large number of clinical studies have
demonstrated the independent role of 123mIBG imaging
in prognosis assessment and risk stratification irrespec-
tive of the etiology of heart failure.4-6 The new solid-
state cardiac cameras based on cadmium-zinc-telluride
(CZT) detectors offer higher photon sensitivity and
spatial resolution compared with standard cameras.7
However, only a few studies have evaluated their
accuracy for myocardial sympathetic innervation imag-
ing8-11 and left ventricular perfusion assessment using
perfusion-gated SPECT.12-14
Due to their dramatically increased energy resolu-
tion, these dedicated cardiac cameras potentially enable
combined assessment of myocardial innervation and
perfusion within a single-imaging session, and with a
limited radiation burden.15 Using successive perfusion
and innervation imaging, Gimelli et al8,9 demonstrated a
Figure 1. Anthropomorphic torso phantom (Data Spectrum, Hillsborough, NC) with two fillablecardiac defects: one (13 mL) always filled with cold water (mimicking a matched defect) and one(5.4 mL) filled with 99mTc when 99mTc solution was in the cardiac insert (mimicking a mismatcheddefect).
correlation between the impairment of innervation, rest
perfusion, and mechanical dyssynchrony. Bellevre
et al11 using 99mTc-tetrofosmin to localize the heart
within the thorax, recently demonstrated the feasibility
of determining the late heart-to-mediastinum ratio of123I-mIBG uptake using dual-isotope imaging with a
CZT camera (DSPECT) in patients with heart failure.
Despite their increased energy resolution, the scatter
fraction remains high with CZT cameras.16 In addition,
the tailing effect in the energy spectrum toward lower
energies due to incomplete charge collection17 may
specifically affect count statistics with CZT cameras.
These two phenomena may impact image acquisition
within the 99mTc photopeak during 123I/99mTc dual-
isotope acquisition, further compromising the accuracy
of left ventricular perfusion assessment using the 99mTc-
labeled tracer. There is a lack of data about the use of
CZT SPECT cameras for simultaneous assessment of
left ventricular innervation and perfusion using123I/99mTc dual-isotope acquisition.
Using an anthropomorphic torso phantom with a
cardiac insert, we aimed to compare cardiac dual-isotope
imaging with separate 123I and 99mTc acquisitions with
simultaneous dual-isotope acquisitions performed using
two commercially available CZT cameras, Discovery
NM 530c (DNM 530c, GE Healthcare, Milwaukee, WI,
USA) and DSPECT (Biosensors International, Caesarea,
Israel).
METHODS
Phantom Studies
We used an anthropomorphic torso phantom (Data
Spectrum, Hillsborough, NC) containing a cardiac insert
(Figure 1). Two fillable defects were used inside the cardiac
Blaire et al. Journal of Nuclear Cardiology!
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33
insert to mimic a matched and a mismatched defect, respec-
tively, in the septum and the lateral wall. The phantom was
successively filled with a solution of 123I alone, 99mTc alone,
and a mixture of 123I and 99mTc. The characteristics and
activities of each cardiac phantom are presented in Table 1.
The liver and mediastinum compartments were filled with 123I
and/or 99mTc solutions as previously described.18 Radioactivity
concentrations were chosen to mimic known myocardial
activities of 123I-mIBG and 99mTc-tetrofosmin. Three datasets
(single 123I, single 99mTc, and dual 123I and 99mTc) were
acquired using four different acquisition times (7, 11, 22, and
33 minutes) on each camera (DNM 530c and DSPECT). In
addition, a normal phantom database was built using ten
single-isotope (separate 123I and 99mTc) acquisitions performed
with the anthropomorphic torso phantom including the cardiac
insert without any defect for both cameras. The acquisition
times were 5, 7, 10, 11, 12, 15, 17, 20, 22, and 33 minutes,
respectively. The activities were 11 kBq/mL for 123I and 22
kBq/mL for 99mTc.
CZT Cameras
We successively used (i) a DNM 530c equipped with a
multiple pinhole collimator and 19 stationary CZT detectors
that simultaneously image 19 cardiac views, each detector
being composed of four 5-mm-thick elements of 32x32 pixels
(pixel size 2.46 x 2.46 mm)19 and (ii) a DSPECT operating
with 9 mobile blocks of pixelated CZT detectors (pixel size
2.46 x 2.46 mm) associated with a wide-angle square-hole
tungsten collimator, recording a total of 120 projections by
each block.16 The energy window was asymmetric for both
cameras, 140 keV (-10% ? 5%) for 99mTc and 159 keV (-5%
? 10%) for 123I, for each acquisition. No attenuation correc-
tion was performed.
Image Reconstruction
Image reconstruction was performed using dedicated
commercially available software to mimic the routine clinical
conditions. Scatter, crosstalk, and tailing effect were corrected
using the DSPECT solely for dual (and not single)-isotope
acquisitions, according to a validated method.20 No correction
was applied when using the DNM 530c. Reconstruction was
performed using a specific iterative reconstruction algorithm
according to each vendor’s recommendation for clinical use,
leading to a reconstructed pixel size of 4 x 4 x 4 and 4.92 x
4.92 x 4.92 mm, respectively, for DNM 530c and DSPECT,
respectively. Short-axis reconstructed images were analyzed
off-line with commercially available software21 (QPS, Cedars-
Sinai Medical Center, Los Angeles, CA), using the dedicated
normal phantom databases and a 17-segment model of the left
ventricle.
Image Analysis
The segmental activity (expressed in percent of the
maximal myocardial activity) for 123I and 99mTc in separate Table
1.Anthropomorphic
torsophantom
withtw
ofillable
cardiacdefects:activitiesforsingle
123I(row
#1),single
99mTc(row
#2),and
simultaneousdual123Iand
99mTcacquisitions(row
#3)
Phanto
mCard
iac
insert
Septaldefect
(13mL)
Lateral
defect(5.4
mL)
Liver
Mediastinum
#1
123I
(11kBq/m
L)
Cold
water
Cold
water
123I
(17.5
kBq/m
L)
123I
(0.6
kBq/m
L)
#2
99mTc
(22kBq/m
L)
Cold
water
99mTc
(22kBq/m
L)
99mTc
(35kBq/m
L)
99mTc
(1.2
kBq/m
L)
#3
123I/99mTc
(11/2
2kBq/m
L)
Cold
water
99mTc
(22kBq/m
L)
123I/99mTc
(17.5/3
5kBq/m
L)
123I/99mTc
(0.6/1
.2kBq/m
L)
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and simultaneous dual-isotope (123I and 99mTc) acquisitions
was analyzed. The results provided are related to the average
of the four acquisition times.
The extent of 123I and 99mTc activity defects was
delineated on bull’s eye polar maps using a 50% level
isocontour and was quantified as a percentage of the ventric-
ular surface. The mismatch extent was assessed as the
proportion of the myocardial surface with a 123I relative
uptake below the 50% threshold and a 99mTc relative uptake
above the 50% threshold.
Finally, contrast (%) was measured in one reconstructed
midventricular small-axis slice using the imageJ software22 by
use of the count ratio (i) between the defect and the normal
myocardium [Defect contrast = 100*|Cdefect - Cnormal|/(Cde-
fect ? Cnormal)] and (ii) between the normal myocardium and
the ventricular cavity [Image contrast = 100*|Cnormal - Ccav-
ity|/(Cnormal ? Ccavity)], where Cdefect, Cnormal, and Ccavity stand
for the mean reconstructed counts in a 2 9 2-pixel region of
interest (ROI), respectively, traced within the myocardial
defect (septal and lateral), the normal myocardial wall, and the
ventricular chamber.
Statistical Analysis
Continuous variables are presented as mean ± standard
deviation (mean ± SD). The effect of camera (DNM 530c vs
DSPECT), acquisition mode (single vs dual isotope), isotope
(123I and 99mTc), and the interaction between camera type and
isotope was evaluated using a linear model analysis with a
least squares fit. Concordance and agreement between single-
isotope activity (separate 123I and 99mTc acquisitions) and
simultaneous dual-isotope activity (123I and 99mTc) on DNM
530c and DSPECT were tested using Lin’s concordance
correlation coefficient (CCC)23 and Bland–Altman analysis,24
respectively. Lin’s CCC is essentially equivalent to the kappa
coefficient but is applicable to continuous data. It evaluates
both accuracy and precision, indicating how far the measure-
ment pairs are away from the line of identity. Paired
continuous data were compared using a paired t-test. A two-
tailed P value B .01 was considered as statistically significant.
Statistical analysis was performed using R software version
3.2.4 (R Foundation for Statistical Computing, Vienna, Aus-
tria) and JMP! version 11.0 (SAS Institute Inc., Cary, NC).
RESULTS
Assessment of Tracer Activity
The mean segmental activities obtained from sin-
gle- (separate 123I and 99mTc acquisitions) and
simultaneous dual-isotope (123I and 99mTc) acquisitions
for both energy windows (123I and 99mTc) are presented
in Figure 2. The 99mTc activity value was significantly
impacted by the acquisition mode (single vs dual) for
both DNM 530c (P\ .0001) and DSPECT (P\ .001),
but not the 123I activity value (NS). Comparing the two
cameras, the mean 123I activity value was significantly
increased using the DSPECT compared to DNM 530c
with both single- (P\ .0001) and simultaneous dual-
isotope acquisition (P\ .0001).
With both DNM 530c and DSPECT (Figure 3),
Lin’s CCC demonstrated an almost perfect concordance
between reconstructed segmental activities from serial
single-isotope and simultaneous dual-isotope acquisi-
tions. Bland–Altman analysis confirmed the excellent
agreement between single- and dual-isotope acquisitions
for each camera type. When comparing the results
between DNM 530c and DSPECT (Figure 4), Lin’s
Figure 2. Segmental relative activities on DNM 530c (A) and DSPECT (B) using a 17-segmentmodel with single (separate 123I and 99mTc) acquisitions compared with simultaneous dual-isotope(123I and 99mTc) acquisitions for both energy windows (123I and 99mTc) expressed as mean value ±standard deviation. *P\ .001 vs dual, **P\ .0001 vs DSPECT.
Blaire et al. Journal of Nuclear Cardiology!
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35
0 20 40 60 80 100
-40
-20
02
04
0
Mean uptake DSPECT [(123I+dual123I)/2] (%)
Diffe
ren
ce
up
take
DS
PE
CT
[1
23
I-d
ua
l12
3I]
(%
)
Mean difference : -1.65 (95% CI: -16.7 ; 13.41)
+/- 2SD
y = 0.082 x + -6.042 ; R2 = 0.044
0 20 40 60 80 100
-40
-20
02
04
0
Mean uptake [(DNM 123I+ DNM Dual 123I)/2] (%) D
iffe
ren
ce
up
take
[D
NM
12
3I-
DN
M D
ua
l 1
23
I] (
%)
Mean difference : -1.54 (95% CI: -13.78 ; 10.69)
+/- 2SD
y = -0.06 x + 1.271 ; R2 = 0.038
DNM 123I uptake (%)
DN
M D
ual 123I upta
ke (
%)
Line of perfect concordance
Reduced major axis
CCC: 0.95 (95% CI 0.92 - 0.97)
020
40
60
80
100
020
40
60
80
100
02
04
06
08
01
00
DNM 99mTc uptake (%)
DN
M D
ua
l 9
9m
Tc u
pta
ke
(%
)
Line of perfect concordance
Reduced major axis
CCC: 0.97 (95% CI 0.96 - 0.98)
0 20 40 60 80 100
-40
-20
02
04
0
Mean uptake [(DNM 99mTc+ DNM Dual 99mTc)/2] (%)
Diffe
ren
ce
up
take
[D
NM
99
mT
c-D
NM
Du
al 9
9m
Tc]
(%)
Mean difference : -2.09 (95% CI: -10.37 ; 6.19)
+/- 2SD
y = 0.051 x + -4.853 ; R2 = 0.056
0 20 40 60 80 100
0 20 40 60 80 100
0 20 40 60 80 100
DSPECT 123I uptake (%)
DS
PE
CT
Du
al 1
23
I u
pta
ke
(%
)
Line of perfect concordance
Reduced major axis
CCC: 0.92 (95% CI 0.88 - 0.95)
A
B
C
Figure 3. Lin’s concordance correlation coefficients and Bland–Altman analysis for the compar-ison between simultaneous dual-isotope acquisition and single separate acquisition for each isotope(123I and 99mTc) using DNM 530c (A, B) and DSPECT (C, D), respectively. All P values = NS.
Journal of Nuclear Cardiology! Blaire et al.
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36
CCC and Bland–Altman analysis also demonstrated
strong agreement between the two cameras for both
single- and simultaneous dual-isotope acquisition.
Mismatch Between 123I and 99mTc Activities
Defect and mismatch size delineated on bull’s eye
polar maps comparing single separate acquisition and
simultaneous dual-isotope acquisition for each isotope
(123I and 99mTc) using DNM 530c and DSPECT are
presented in Figure 5 and Table 2. As illustrated in
Table 2, the mismatch was larger using DNM 530c
compared to DSPECT. However, this difference was not
statistically significant using linear model analysis that
showed no impact of camera type and acquisition time
on the size of activity defects and mismatch (P = NS).
Image Contrast
Image and defect contrasts comparing single- and
simultaneous dual-isotope acquisition for each isotope
(123I and 99mTc) using both cameras are illustrated,
respectively, in Figure 6A and B. As shown in Fig-
ure 6A, there was a significant decrease of 123I image
contrast using dual-isotope acquisition with the DNM
530c (P\ .0001) compared to single-isotope acquisi-
tion. On the other hand, using the DSPECT, image
contrast significantly increased with both 99mTc and 123I
using dual-isotope acquisition (P\ .0001). However,
there was no significant difference between single- and
dual-isotope acquisitions regarding defect contrast for
both camera and both isotope (Figure 6B, all P
values = NS).
DISCUSSION
This phantom study was designed to mimic the
combined evaluation of left ventricular perfusion and
innervation by means of an anthropomorphic torso
phantom with a cardiac insert, imaged using the two
commercially available CZT cameras. Although there
was a significant effect of dual-isotope acquisition on
estimates of 99mTc activity, our results demonstrated that
the size of both 123I and 99mTc defects as well as their
mismatch was impacted neither by the type of camera
(DSPECT vs DNM 530c), nor by the acquisition mode
(single vs dual) or by the acquisition time. To our
knowledge, this is the first dual-isotope torso phantom
study assessing perfusion (99mTc) and innervation (123I)
using two commercially available CZT cameras (DNM
530c and DSPECT). Our results also suggested that a
dual 123I-99mTc acquisition does not compromise the
assessment of ventricular perfusion using the 99mTc
photopeak in comparison with a single 99mTc
acquisition.
In the clinical setting, simultaneous dual-radionu-
clide acquisition provides perfectly registered functional
images within a reduced imaging time. Using conven-
tional Anger cameras, several dual-radionuclide SPECT
imaging protocols have been proposed. Simultaneous99mTc-sestamibi/123I-BMIPP imaging was used for
DSPECT 99mTc uptake (%)
DS
PE
CT
Du
al 9
9m
Tc u
pta
ke
(%
)
Line of perfect concordance
Reduced major axis
CCC: 0.96 (95% CI 0.94 - 0.97)
0 20 40 60 80 100
-40
-20
02
04
0 Mean uptake
[(DSPECT 99mTc+ DSPECT Dual 99mTc)/2] (%)
D
iffe
ren
ce
up
take
[DS
PE
CT
99
mT
c-D
SP
EC
T D
ua
l 9
9m
Tc] (%
) Mean difference : -2.43 (95% CI: -13.56 ; 8.7)
+/- 2SD
y = 0.002 x + -2.531 ; R2 = 0
D
02
04
06
08
01
00
0 20 40 60 80 100
Figure 3. continued.
Blaire et al. Journal of Nuclear Cardiology!
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37
A
B
C
0 20 40 60 80 100
-40
-20
02
04
0
Diffe
rence u
pta
ke [D
SP
EC
T D
ual 123I-
DN
M D
ual 123I]
(%
)
Mean difference : 6.53 (95% CI: -11.95 ; 25.01)
+/- 2SD
y = -0.106 x + 11.933 ; R2 = 0.048
DN
M D
ua
l 1
23
I u
pta
ke
(%
)
Line of perfect concordance
Reduced major axis
CCC: 0.84 (95% CI 0.77 - 0.9)
0 20 40 60 80 100
-40
-20
02
04
0
Mean uptake [(DSPECT 99mTc+ DNM 99mTc)/2] (%)
Diffe
rence u
pta
ke [
DS
PE
CT
99m
Tc-D
NM
99m
Tc] (%
)
Mean difference : 2.32 (95% CI: -18.37 ; 23.01)
+/- 2SD
y = 0.078 x + -1.934 ; R2 = 0.023
DSPECT 99mTc uptake (%)
DN
M 9
9m
Tc u
pta
ke (
%)
Line of perfect concordance
Reduced major axis
CCC: 0.87 (95% CI 0.8 - 0.92)
0 20 40 60 80 100
-40
-20
02
04
0
Mean uptake [(DSPECT 123I+ DNM 123I)/2] (%) D
iffe
ren
ce
up
take
[D
SP
EC
T 1
23
I-D
NM
12
3I]
(%
)
Mean difference : 6.43 (95% CI: -9.79 ; 22.65)
+/- 2SD
y = 0.039 x + 4.496 ; R2 = 0.009
DSPECT 123I uptake (%)
DN
M 1
23
I u
pta
ke
(%
)
Line of perfect concordance
Reduced major axis
CCC: 0.87 (95% CI 0.81 - 0.92)
0 20 40 60 80 100
0 20 40 60 80 100
0 20 40 60 80 100
020
40
60
80
100
020
40
60
80
100
020
40
60
80
100
Mean uptake [(DSPECT Dual 123I+ DNM Dual 123I)/2] (%) DSPECT Dual 123I uptake (%)
Figure 4. Lin’s concordance correlation coefficients and Bland–Altman analysis for the compar-ison between the 2 CZT cameras for both isotope (123I and 99mTc) and acquisition mode (singleseparate acquisitions (A, B) and simultaneous dual-isotope acquisition (C, D), respectively). All Pvalues = NS.
Journal of Nuclear Cardiology! Blaire et al.
A phantom study
Author's personal copy
38
assessing rest perfusion and fatty acid metabolism at the
same time in patients with recent myocardial infarc-
tion.25,26 Using the conventional Anger camera, the
simultaneous dual-isotope acquisition using 201Tl and123I-mIBG is well documented and widely used, with
possible scatter and crosstalk correction.27 A combined
perfusion and sympathetic innervation imaging with
serial 123I-mIBG and 99mTc-labeled tracers enables the
evaluation of innervation-perfusion mismatch and may
provide valuable information to assess the extension of
the trigger zone as a prognostic factor of the ventricular
arrhythmia in infarcted myocardium.2,28 In addition,
Gimelli et al,8,9 using the DNM 530c camera and a
sequential 123I-mIBG and 99mTc-tetrofosmin myocardial
SPECT, demonstrated a relevant association between
innervation derangement, impaired myocardial perfu-
sion, and mechanical dyssynchrony. Dual-isotope
acquisition with CZT cameras remains a challenging
technique. Impaired myocardial innervation leads to low
myocardial 123I-mIBG uptake, requiring a dual-isotope
protocol to localize the heart.11 Due to the small field-of-
view of the dedicated CZT cardiac cameras, a scout
view is mandatory to localize the heart and correctly
center the field-of-view prior to SPECT acquisition. In
addition, most of the patients referred for 123I-mIBG
assessment have an ischemic cardiomyopathy with heart
failure (66% in the ADMIRE-HF study6). In this clinical
setting, the dual-isotope protocol allows a simple and
efficient co-registration of innervation and perfusion
studies, and thus a robust assessment of innervation-
perfusion mismatch. The measurement of myocardial
innervation and perfusion is a key step of prognosis
assessment and may potentially be altered when using
CZT cameras with a simultaneous dual-isotope protocol
due to down-scatter, crosstalk, and tailing effect of 123I
in the 99mTc photopeak.
Despite a significant increase in energy resolution
and sensitivity, the scatter fraction remains high with
CZT cameras (30% vs 34% with conventional Anger
gamma cameras).16 Due to incomplete charge collection
and inter-crystal scatter, the CZT detectors are subjected
to a tailing effect at the lower part of the photopeak that
may lead to an over-correction of photon scatter, when
using multiple energy windows methods.20 Recently,
Fan et al with a DNM 530c29 and Holstensson et al with
a DSPECT30 presented a model-based correction algo-
rithm which extracts the useful primary counts of 99mTc
and 123I from projection data, taking into account the
tailing effect to correct for scatter and crosstalk in99mTc-123I dual imaging. In our study, all reconstruc-
tions were performed using the vendor’s workstation
and commercially available software for both cameras.
Routinely, scatter, crosstalk, and tailing effect correc-
tions29 were not available for the DNM 530c. On the
other hand, image data from DSPECT were corrected
for scatter, crosstalk, and tailing effect using a previ-
ously described method.20 The ratio between 123I and99mTc activity concentrations was set to 1:2, which is
representative of the low 123I-mIBG myocardial uptake
observed in patients with heart failure. Under these
conditions, the absence of corrections when using the
DNM 530c did not affect the assessment of 99mTc defect
size with simultaneous dual 99mTc-123I acquisition
compared to single 99mTc acquisition.
D
0 20 40 60 80 100
-40
-20
02
04
0 Mean uptake
[(DSPECT Dual 99mTc+ DNM Dual 99mTc)/2] (%)
D
iffe
ren
ce
up
take
[D
SP
EC
T D
ua
l 9
9m
Tc-D
NM
Du
al 9
9m
Tc]
(%)
Mean difference : 2.66 (95% CI: -22.2 ; 27.53)
+/- 2SD
y = 0.134 x + -4.942 ; R2 = 0.043
DSPECT Dual 99mTc uptake (%)
DN
M D
ua
l 9
9m
Tc u
pta
ke
(%
)
Line of perfect concordance
Reduced major axis
CCC: 0.8 (95% CI 0.7 - 0.87)
0 20 40 60 80 100
02
04
06
08
01
00
Figure 4. continued.
Blaire et al. Journal of Nuclear Cardiology!
A phantom study
Author's personal copy
39
D’Estanque et al31 recently reported the impact of
scatter correction in dual-isotope (201Tl/123I-mIBG)
cardiac SPECT protocols for trigger zone assessment
with the DNM 530c. This correction improved the
accuracy of myocardial SPECT for mapping the seg-
mental myocardial sympathetic denervation. In their
study, perfusion was assessed using Thallium, which
energy window was centered at 67 keV ± 10%, right in
the 123I down-scatter and crosstalk window. The contri-
bution of tailing and down-scatter photons from the
photopeak of 123I, detected as primary photons in the99mTc energy window is less important than in the 201Tl
energy window, as depicted in Figure 7. According to
D’Estanque et al, scatter correction is required when
using 201Tl/123I-mIBG.
Although only the possible evaluation with and
without scatter correction could help better understand
the need or not to use scatter for the DNM 530c, our
results suggest that correction for crosstalk, scatter, and
tailing effect of 123I in the 99mTc photopeak may likely
have only limited clinical relevance in patients with
ischemic heart disease.
The availability of tailing effect correction using the
DSPECT camera only for dual (and not single)-isotope
acquisitions20 may explain the difference in terms of
image contrast between single-isotope (separate 123I and99mTc acquisitions) and simultaneous dual-isotope (123I
and 99mTc) acquisitions with the DSPECT. This led to a
higher image contrast for both 123I and 99mTc images
when using a simultaneous dual-isotope acquisition with
the DSPECT compared to single-isotope acquisition.99mTc crosstalk into the 123I window is negligible when
performing a simultaneous CZT acquisition.20
LIMITATIONS OF THE STUDY
As reconstructions were performed according to
each manufacturer’s recommendations, scatter, cross-
talk, and tailing effect corrections were available with
the DSPECT but not with the DNM 530c camera.
However, our results showed no critical differences
between the single- and dual-isotope conditions for the
assessment of 99mTc images, even with the DNM 530c.
At best, the demonstration could be made by comparing
the results obtained with and without corrections.29,30
However, the aim of our study was to compare the
results obtained with the two CZT cameras using the
dedicated commercially available software to mimic
routine clinical conditions. Finally, our results were
obtained using specific reconstruction and filtering
algorithms recommended by the manufacturers for
clinical use and cautions are required in case of using
different algorithms in order to achieve successful
assessment.Table
2.Defectandmismatchsizedelineatedonbull’s
eyepolarmapsusinga50%
levelisocontourandquantifiedasapercentageof
theventricularsu
rfacewithsingle-iso
topecompared
withsimultaneousdual-isotopeacquisitionsforboth
energywindows(1
23Iand
99mTc)onDNM
530candDSPECT
Camera
DNM
530c
DSPECT
Acquisitiontype
Single
Dual
Single
Dual
Energywindow
123I
99mTc
Mismatch
123I
99mTc
Mismatch
123I
99mTc
Mismatch
123I
99mTc
Mismatch
7-M
inacquisition
26
21
528
20
826
20
626
20
6
11-m
inacquisition
27
20
726
21
526
20
624
20
4
22-M
inacquisition
27
19
828
19
927
22
526
20
6
33-M
inacquisition
27
19
827
20
725
21
426
21
5
Mean±SD
(%)
26.8
±0.5
19.8
±0.9
7.0 ±1.4
27.3
±0.9
20
±0.8
7.3 ±1.7
26.0
±0.8
20.8
±1.0
5.3 ±1.0
25.5
±1.0
20.3
±0.5
5.3 ±0.9
AllPvalues=
NS
Journal of Nuclear Cardiology! Blaire et al.
A phantom study
Author's personal copy
40
Figure 5. Single-isotope (separate 123I and 99mTc) acquisitions and mismatch on DNM 530c (A)and DSPECT (C) and simultaneous dual-isotope (123I and 99mTc) acquisitions and mismatch onDNM 530c (B) and DSPECT (D) presented as the bull’s eye polar maps of the 22-min acquisitions.
Blaire et al. Journal of Nuclear Cardiology!
A phantom study
Author's personal copy
41
NEW KNOWLEDGE GAINED
With an increased energy resolution, the CZT
cameras may allow, under routine conditions, a simul-
taneous and accurate segmental study of myocardial
innervation and perfusion (match and mismatch).
CONCLUSION
In this phantom study, the two CZT cameras (DNM
530c and DSPECT) provided similar results in the
evaluation of regional myocardial innervation and per-
fusion match and mismatch with single- (separate 123I
BA
*
*
*
60
65
70
75
80
85
90
95
100
single dual
Imag
e co
ntr
ast
(%)
60
65
70
75
80
85
90
95
100
single dual
Def
ect
contr
ast
(%)
Figure 6. Image (A) and defect (B) contrasts with single (separate 123I and 99mTc) acquisitionscompared with simultaneous dual-isotope (123I and 99mTc) acquisitions for both energy windows(123I and 99mTc) on DNM 530c and DSPECT expressed as mean value ± standard deviation.*P\ .0001 vs dual.
a
Energy (keV)
b
Energy (keV)
0
20
40
60
80
100
30 80 130 180
0
20
40
60
80
100
30 80 130 180
No
rmal
ised
cou
nts
No
rmal
ised
cou
nts
123I and 99mTc99mTc123IA B
Figure 7. Single-isotope (separate 123I and 99mTc) and simultaneous dual-isotope (123I and 99mTc)acquisitions on DNM 530c (A) and DSPECT (B) presented as the energy spectra of the 7-minacquisitions.
Journal of Nuclear Cardiology! Blaire et al.
A phantom study
Author's personal copy
42
and 99mTc acquisitions) and simultaneous dual-isotope
(123I and 99mTc) acquisitions. These findings may have
diagnostic and therapeutic implications in heart failure
patients referred for a combined assessment of perfusion
and innervation.
Acknowledgment
Nathaniel Roth, Rafael Baavour, Sylvie Petit, Mathilde
Thelu, and the nuclear medicine technicians at Caen and Lille
for their technical assistance.
Disclosures
The authors have indicated that they have no financial
conflict of interest.
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V. :Déterminationdurapportcardiomédiastinaldela
fixationd’123I-MIBGlorsd’acquisitionsTEMPdouble-isotope
(123I-MIBG/99mTc-tétrofosmine)surunegamma-caméraCZTà
collimationmulti-sténopéechezlespatientsporteurs
d’insuffisancecardiaque
A. RésuméLebutdecetteétuderétrospectiveétaitdedéterminerleRCMdelafixationdel’123I-MIBG
obtenu à l'aide d'une gamma-caméra à semi-conducteurs CZT à collimation multi-
sténopée (la DNM 530c) et de le comparer aux RCM obtenus en utilisant l'imagerie
planaireconventionnelle(Infinia,GEHealthcare,Milwaukee,WI,USA).
Méthode:Quarantepatientsconsécutifssouffrantd'insuffisancecardiaqueontbénéficié
d’uneacquisitionplanaire4haprèsinjectiond’123I-MIBG(191±41MBq).Pourlocaliser
lecœurenutilisantlaDNM530c,uneactivitéde99mTc-tétrofosmine(358±177MBq)a
étéadministréeetuneacquisitiondouble-isotopeaétéeffectuée.LesRCMontétécalculés
(i) avec une imagerie planaire conventionnelle (HMRplanar), (ii) avec des images de
reprojectionantérieure(HMRreproj)et(iii)avecdesimagesreconstruitestransaxiales
enutilisantlaDNM530c(HMRtransaxial).Dansuneétudesurfantômeanthropomorphe
detorse,nousavonsdéfiniunmodèle linéaireadaptant lesrésultatsCZTauxdonnées
planaires.CemodèleaensuiteétéappliquépourfournirlesvaleursdeRCMCZTcorrigées
chezlespatients(respectivementcHMRreprojetcHMRtransaxial).
Résultats:Trente-quatrehommeset6femmes(71±9ans)souffrantd’uneinsuffisance
cardiaque d’origine ischémique (22 patients) et non ischémique (18 patients) ont été
inclusdansl'étude.Vingt-deuxdes40patients(55%)présentaientuneclasseIIdelaNew
York Heart Association et la fraction d'éjection était de 35 ± 9%. En comparaison à
HMRplanar(1,44±0,14),HMRreproj(1,12±0,19)etHMRtransaxial(1,35±0,34)étaient
diminué (p <0,0001 et p <0,01 respectivement). cHMRreproj (1,54 ± 0,09) et
cHMRtransaxial (1,45 ± 0,14) étaient significativement différents (p <0,0001). Le
coefficient de corrélation de concordance de Lin et l'analyse de Bland-Altman ont
démontréuneconcordancepresqueparfaiteetunagrémentélevéentreHMRplanaret
cHMRtransaxial(p=NS)enutilisantlesimagestransaxialesreconstruitesmaispasavec
cHMRreprojenutilisantdesimagesdereprojectionplanaire(p<0,0001).
45
Conclusion:CetteétudeadémontréqueladéterminationduRCMtardifdelafixation
cardiaque d’123I-MIBG en utilisant l'acquisition double-isotope (123I et 99mTc) sur une
caméra CZT à collimationmulti-sténopée (DNM-530c) est réalisable chez les patients
souffrantd'insuffisancecardiaque.Cependant,cettedéterminationdoitêtreeffectuéeen
utilisant les images transaxiales reconstruites etune correction linéairebasée surdes
donnéesd’acquisitionsdefantômes.
Communicationsorales:
*SNM2017,Denver
Publication:acceptéeparleJNM2017
46
Doi: 10.2967/jnumed.117.194373Published online: June 23, 2017.J Nucl Med.
Tanguy Blaire, Alban Bailliez, Fayçal Ben Bouallègue, Dimitri Bellevre, Denis Agostini and Alain Manrique heart failure
Tc-tetrofosmin) multi-pinhole CZT SPECT in patients with99mI-MIBG/123dual-isotope (I-MIBG uptake using123Determination of the heart-to-mediastinum ratio of
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B. Publicationcorrespondante(JNuclMed,2017)
47
1
Determination of the heart-to-mediastinum ratio of 123
I-MIBG uptake using dual-
isotope (123
I-MIBG/99m
Tc-tetrofosmin) multi-pinhole CZT SPECT in patients with
heart failure.
Tanguy Blaire1,2,3
, Alban Bailliez1,2,3
, Fayçal Ben Bouallegue4, Dimitri Bellevre
5, Denis Agostini
2,5, Alain Manrique
2,5
1 Department of Nuclear Medicine, UF 5881, Groupement des Hôpitaux de l’Institut Catholique de Lille, Lomme, France
2 Normandie Univ, UNICAEN, Signalisation, électrophysiologie et imagerie des lésions d'ischémie-reperfusion myocardique, 14000
Caen, France
3 Department of Nuclear Medicine, IRIS, Polyclinique du Bois, Lille, France
4 Department of Nuclear Medicine, CHU de Montpellier, France
5 Department of Nuclear Medicine, CHU Cote de Nacre, Caen, France
Corresponding Author, scientist in training: Tanguy Blaire, MD, Department of Nuclear Medicine, UF 5881, Groupement des
Hôpitaux de l’Institut Catholique de Lille, Lomme, France
Tel: (+33) 320 001 655, Fax: (+33) 320 098 010,
Email: [email protected]
Word counts: Abstract: 285 words; Article: 5029
Running title: 123
I-MIBG HMR using CZT SPECT
Financial support: No
48
2
ABSTRACT
The aim of this retrospective study was to determine the heart-to-mediastinum ratio (HMR) of
123I-metaiodobenzylguanidine (MIBG) uptake obtained using a multi-pinhole cadmium-zinc-
telluride (CZT)-based camera (Discovery NM 530c, DNM-530c, GE Healthcare, Milwaukee, WI,
USA) in comparison with that obtained using conventional planar imaging (Infinia, GE
Healthcare, Milwaukee, WI, USA). Methods: Forty consecutive heart failure patients underwent
planar acquisition 4 h after 123
I-MIBG injection (191±41 MBq). To localize the heart using DNM-
530c, 99m
Tc-tetrofosmin (358±177 MBq) was administered and a dual-isotope acquisition was
performed. The HMRs were calculated (i) with conventional planar imaging (HMRplanar), (ii) with
anterior reprojection images (HMRreproj) and (iii) with transaxial reconstructed images using
DNM-530c (HMRtransaxial). In a phantom study, we estimated a linear model fitting the CZT to the
planar data that was further applied to provide corrected CZT HMR values in patients (cHMRreproj
and cHMRtransaxial respectively). Results: Thirty-four men and 6 women (71±9 y/o) with ischemic
(22 patients) and nonischemic (18 patients) heart failure completed the study. Twenty-two of the
40 patients (55%) were New York Heart Association class II, and ejection fraction was 35±9 %.
Compared to HMRplanar (1.44±0.14), HMRreproj (1.12±0.19) and HMRtransaxial (1.35±0.34) were
decreased (p<0.0001 and p<0.01 respectively). Corrected cHMRreproj (1.54±0.09) and
cHMRtransaxial (1.45±0.14) were different (p<0.0001). Lin’s concordance correlation and Bland-
Altman analysis demonstrated an almost perfect concordance and a high agreement between
HMRplanar and cHMRtransaxial (p=NS) using transaxial reconstructed images but not with cHMRreproj
using reprojection images (p<0.0001). Conclusion: This study demonstrated that determination
of late HMR of cardiac 123
I-MIBG uptake using dual-isotope (123
I and 99m
Tc) acquisition on a
multi-pinhole CZT camera (DNM-530c) is feasible in patients with heart failure. However, this
determination should be performed using transaxial reconstructed images and a linear correction
based on phantom data acquisitions.
Keywords CZT, DNM-530c, MIBG, Heart-to-mediastinum ratio, heart failure, dual-isotope
49
3
INTRODUCTION
Impairment of cardiac sympathetic innervation assessed with 123
I-MIBG is recognized as an
independent prognostic factor in patients with heart failure (1-6). The late HMR of 123
I-MIBG is
a major predictor of sudden death and cardiac events in patients with heart failure. A HMR below
1.6 is associated with an increased risk. (6). Currently, the calculation of HMR requires a planar
static image of the thorax. This technique is well-standardized and reproducible using a
conventional Anger camera (7,8). Recently, dedicated cardiac single photon emission computed
tomography (SPECT) cameras using CZT detectors have dramatically transformed the routine of
myocardial perfusion imaging in patients with known or suspected coronary artery disease. These
cameras have a better count detection sensitivity resulting in decreased acquisition times and
injected radiopharmaceutical doses, and improved energy resolution, permitting better photon
energy discrimination for dual-isotope imaging.
Myocardial perfusion imaging obtained using cardiac CZT cameras is well validated
against the conventional Anger camera for the diagnosis of coronary artery disease (9-12). Only a
few studies have evaluated myocardial sympathetic innervation imaging with these new
generation detectors (13-16). With DNM-530c, Gimelli et al. (13,14) assessed regional left
ventricular denervation, while D’Estanque et al. (15) reported the impact of scatter correction in
dual-isotope (201
Tl/123
I-MIBG) cardiac SPECT protocols for trigger zone assessment defined as
areas of autonomic nervous system dysfunction in viable myocardium that may contribute to the
genesis of ventricular arrhythmia. In the Adrecard study, Bellevre et al. (16) recently demonstrated
that the determination of late HMR of 123
I-MIBG was feasible in patients with heart failure using
a parallel collimator CZT camera (DSPECT, Biosensors International, Caesarea, Israel). The two
commercially available CZT cameras differ for sensitivity (4-fold improved with DNM-530c, and
nearly 7-fold with DSPECT), and spatial resolution (6.7 mm with DNM-530c, and 8.6 mm with
DSPECT) leading to images with different sharpness and contrast-to-noise ratios (11,17,18). Until
now, there have been no reports on the use of the DNM-530c, a multi-pinhole CZT SPECT
camera, for determining HMR of 123
I-MIBG uptake. As previously emphasized (19,20),
quantification of HMR is influenced by the type of collimators used and the number of scattered
photons. Consequently, the value of HMR is expected to depend on the type of CZT camera used,
hence the need for a study to validate the multi-pinhole dedicated cardiac CZT camera.
The aim of this study was to compare the late HMR of 123
I-MIBG uptake determined using
dual-isotope CZT acquisition (DNM-530c) with that determined using conventional planar
imaging in patients with heart failure.
50
4
MATERIALS AND METHODS
Phantom Studies
To estimate the effectiveness of the DNM-530c camera in measuring HMR, we performed
several phantom acquisitions using an anthropomorphic torso phantom (Data Spectrum,
Hillsborough, NC) with a cardiac insert. The liver and mediastinum compartments were filled with
20 MBq (17.5 kBq/mL) and 5 MBq (0.6 kBq/mL) 123
I activities, respectively. Ten consecutive
acquisitions were performed over 10 min using a conventional Anger camera (Infinia) and a CZT-
camera (DNM-530c). The cardiac insert was repeatedly unloaded from 1.75 (11 kBq/mL), to1.5,
1.25, 1.1, 0.94, 0.75, 0.5, 0.35, 0.25 and 0.1 MBq respectively to obtain a wide range of HMRs of
123I , as previously described (16,20).
Patient Population
This retrospective study was approved by our Hospital Ethics Committee for Medical
Research (CIER # 03/01/2016, France). Informed signed consent was obtained from all patients.
Data from 40 consecutive patients with clinically stable ischemic or nonischemic heart failure (left
ventricular ejection fraction, LVEF, <45 %) referred to our institution from May 2011 to May
2016, were retrospectively evaluated. Patients with a recent (<21 days) history of unstable angina
or acute myocardial infarction were excluded from the study.
Conventional Anger Camera Protocol (Planar)
The imaging protocol (Figure 1) was performed according to the recommendations of the
EANM Cardiovascular Committee and the European Council of Nuclear Cardiology (7). 123
I-
MIBG (191±29 MBq depending on the patient’s weight) was administered 30 min after blockade
of the thyroid by oral administration of Lugol solution. Four hours after injection, the late planar
image was first obtained on the conventional gamma camera system, a dual head gamma camera
(Infinia) equipped with low-energy high-resolution collimators. Planar images were acquired in
the anterior view over 10 min (128 × 128 matrix), using a symmetric energy window (159 ± 10
keV).
Dual-isotope (123
I-MIBG/99m
Tc-tetrofosmin) CZT Acquisition Protocol (DNM-530c)
99mTc-tetrofosmin (358±177 MBq) was administered for myocardial perfusion imaging in
order to localize the heart within the thorax. After 15 min, the 99m
Tc image helped to focus the
51
5
detectors on the cardiac area. A 10-min list-mode simultaneous dual radionuclide (99m
Tc and 123
I)
gated scan was then performed using a dedicated CZT cardiac SPECT camera (DNM-530c).
DNM-530c is equipped with 19 stationary CZT detectors, each equipped with a pinhole
collimator, that simultaneously image 19 cardiac views, each detector being composed of four 5-
mm-thick elements of 32x32 pixels (pixel size 2.46 x 2.46 mm) (17). List-mode acquisition
permits the retrospective selection of 99m
Tc and 123
I energy windows, respectively set to 140 keV
(-10 to +5 %) and 159 keV (-5 to +10 %). No scatter correction was performed. Previous studies
using phantom data acquired separately for 99m
Tc and 123
I showed that 99m
Tc crosstalk into the 123
I
window was negligible when performing a simultaneous CZT SPECT acquisition (21,22). To
make sure that different 99m
Tc:123
I ratios do not impact on energy resolution, a set of energy spectra
(single 123
I, single 99m
Tc, dual 123
I-99m
Tc) was acquired using linear sources with three 99m
Tc:123
I
ratios (0.5:1, 1:1, and 5:1), with a constant activity of 123
I (24 MBq) (see Figure 2).
Heart-to-mediastinum 123
I-MIBG Uptake Ratio (HMR) Analysis
A HMRplanar was calculated on the planar images. Myocardial and mediastinal counts were
obtained by drawing regions of interest (ROI) manually on the left ventricle and over the upper
mediastinum area (7).
Using SPECT data, two different methods were tested for assessing the heart-to-
mediastinum 123
I-MIBG uptake ratio. First, a HMRreproj was calculated on a reprojected anterior
view from the SPECT images reconstructed using the vendor’s console. The reprojection of
tomographic data assumed an ideal parallel hole collimation and did not simulate attenuation or
scatter. A ROI encompassing the left ventricle was drawn manually on the 99m
Tc-tetrofosmin
images and automatically copied to the 123
I-MIBG images. A mediastinum ROI (42 pixels) was
then drawn on the 123
I-MIBG images.
Second, a HMRtransaxial was calculated using the transaxial reconstructed SPECT images.
A myocardial elliptic volume of interest (VOI) was drawn manually to encompass the whole heart
on the 99m
Tc-tetrofosmin images. This VOI was automatically copied from the 99m
Tc-tetrofosmin
images to the 123
I-MIBG images. A mediastinum VOI (300 voxels) was manually drawn on the
123I-MIBG images.
Heart-to-mediastinum Ratio Correction Factor
Many factors affecting the HMR of 123
I-MIBG uptake differ between the Infinia and
52
6
DNM-530c cameras, including the type of collimator (parallel-hole low-energy high-resolution
with Infinia vs. multi-pinhole with DNM-530c), energy window, energy resolution which is better
with DNM-530c (approximatively 9% with Infinia vs. about 5% with DNM-530c), and detector
material stopping power (84% for 9.5 mm NaI(Tl) vs. 78% for 5 mm CZT for 159 keV photons).
To take into account the difference between DNM-530c and Infinia, a correction factor was
applied to HMR quantification, based on phantom acquisitions. To extract a correction factor from
the analysis, a linear regression equation obtained in the phantom study was used and the
corrected-HMRreproj (cHMRreproj) and the corrected-HMRtransaxial (cHMRtransaxial) calculated for each
patient in the validation group for further comparison with the HMRplanar values (16,23).
LVEF 99m
Tc-tetrofosmin SPECT with DNM-530c
As previously reported (22), the presence of 123
I does not impact on LVEF assessment
within the 99m
Tc energy window in the dual-isotope condition using DNM-530c. Accordingly,
LVEF was assessed using Quantitative Gated SPECT software (QGS, Cedars-Sinai Medical
Center, Los Angeles, CA).
Statistical Analysis
The normal distribution of data was tested with the Shapiro-Wilk test. Paired HMR values
determined using Infinia and DNM-530c were compared using Student’s t test for paired samples.
Correlations between HMRplanar, HMRreproj and HMRtransaxial were assessed using linear regression
and Pearson’s correlation. Concordance between HMRplanar, HMRreproj and HMRtransaxial values was
tested using Lin’s concordance correlation coefficient (CCC) (24) and Bland-Altman analysis
(25). Lin’s CCC is essentially equivalent to the kappa coefficient but is applicable to continuous
data. It evaluates both accuracy and precision, indicating how far the measurement pairs are away
from the line of identity. Lin’s CCC scale ranges from 0 (no agreement) to +1 (perfect agreement),
where 0.21 – 0.40 indicates fair concordance, 0.41 – 0.60 moderate concordance, 0.61 – 0.80
substantial concordance and 0.81 – 1.00 almost perfect concordance. A two-tailed p value ≤0.05
was considered statistically significant. Statistical analysis was performed using R version 3.3.2
(R Foundation for Statistical Computing, Vienna, Austria).
53
7
RESULTS
Phantom Study
The HMR values obtained from the phantom acquisitions are listed in Table 1. The
HMRreproj (2.82±1.5) and HMRtransaxial (3.51±1.94) were increased compared with HMRplanar
(2.34±0.8, p=NS and p=0.01 respectively). However, Bland-Altman plots demonstrated that
HMRreproj and HMRtransaxial values were underestimated for low HMR and overestimated for high
HMR values. The corrections used for the calculation of cHMRreproj and cHMRtransaxial were
determined by linear regression between CZT and planar HMR in the phantom study: cHMRreproj
= 0.4715×HMRreproj + 1.0416 (r= 0.98) and cHMRtransaxial = 0.4106×HMRtransaxial + 0.8987 (r= 0.99)
respectively.
Population
Among the 40 consecutive patients (34 male, 6 female, mean age 71±9 years, mean LVEF:
35%±9) with heart failure included in the study, 22 (55%) had ischemic heart failure, and 18 (45%)
had nonischemic heart failure. Patient characteristics are presented in Table 1. According to the
New York Heart Association functional classification, 13 patients were class I, 22 class II, and 5
class III. End-diastolic and end-systolic volumes, and LVEF obtained using 99m
Tc-tetrofosmin
SPECT were 171±87 mL, 117±67 mL and 36%±17, respectively.
HMR Quantification in Patients: DNM-530c vs. Planar
In our population, the HMRreproj (1.12±0.19) and HMRtransaxial (1.35±0.34) were
significantly lower than HMRplanar (1.44±0.14, p<0.0001 and p<0.05 respectively). Figures 3A and
4A show Lin’s concordance correlation between HMRreproj and HMRplanar (Figure 3A) and between
HMRtransaxial and HMRplanar (Figure 4A), and demonstrate only a fair concordance between
HMRreproj and HMRplanar (CCC= 0.24) and a substantial concordance between HMRtransaxial and
HMRplanar (CCC= 0.61). Bland-Altman plots (Figure 3B and 4B) further demonstrated a poor
agreement between HMRreproj and HMRplanar (3B) and between HMRtransaxial and HMRplanar (4B)
leading to underestimation of values by DNM-530c. Figure 5 displays a case imaged with Infinia
and DNM-530c.
HMR Quantificationin Patients: Corrected DNM-530c vs. Planar
Corrected cHMRreproj (1.54±0.09) but not cHMRtransaxial (1.45±0.14) was significantly
54
8
higher than HMRplanar (1.44±0.14, p<0.0001 and p=NS respectively). As shown in Figure 3C, there
was a moderate concordance between cHMRreproj and HMRplanar (CCC= 0.49) and Bland’s Altman
plots (Figure 3D) showed a moderate agreement between cHMRreproj and HMRplanar. The mean
difference between the HMR values from the two techniques was 0.11, but significantly increased
as a function of the mean HMR value.
In contrast, as shown in Figure 4C, there was an almost perfect concordance between
cHMRtransaxial and HMRplanar (CCC= 0.92). Bland’s Altman plots (Figure 4D) showed high
agreement between cHMRtransaxial and HMRplanar values. The mean difference between the HMR
values from the two techniques was 0.01, with a narrow 95 % confidence interval, and was stable
over the whole range of HMR values.
55
9
DISCUSSION
Late HMR determination using the Anger camera is well standardized and its prognostic
value is widely recognized. In this retrospective study, we determined the HMR of 123
I-MIBG
uptake using a multi-pinhole dedicated cardiac CZT camera (DNM-530c) in patients with heart
failure and low LVEF. To our knowledge, this is the first dual-isotope study combining 123
I-MIBG
and 99m
Tc-tetrofosmin with a multi-pinhole CZT camera in order to assess cardiac neuronal
function in heart failure. Late HMRs (HMRreproj and HMRtransaxial) were significantly lower in
patients compared with planar imaging, but with high agreement with cHMRtransaxial. Our
results are consistent with previous findings from the Adrecard study (16) conducted using another
model of the dedicated cardiac CZT camera with different spatial resolution and sensitivity
(17,26).
Difference Between Planar and CZT SPECT HMR
Firstly, in order to better understand the camera responses in 123
I-MIBG imaging, we
compared planar and DNM-530c phantom acquisitions, and found that the non-corrected HMRs
obtained with the DNM-530c underestimated the low values and overestimated high values of 123
I-
MIBG uptake. Accordingly, HMRs values in patients were significantly lower with the DNM-
530c compared with the Anger camera, as these patients with heart failure had decreased 123
I-
MIBG uptake.
The collimators used and the stopping power of the detector material may impact on the
quantification of 123
I-MIBG HMR (20,27). Inoue et al. (23) found that a correction factor is
necessary to improve exchangeability between the HMR values calculated using ME and low-to-
medium energy collimators. Nakajima et al. demonstrated that the linear regression equation
between low-energy and ME collimators obtained in a phantom study can be used for
standardizing the measurement of HMR in 123
I-MIBG imaging (28-30). In our study, after
correction, there was still a significant difference between cHMRreproj and HMRplanar (p<0.0001),
but there was no difference between cHMRtransaxial and HMRplanar (p=NS).
Using a different model of camera with mobile CZT detector columns and parallel
tungsten collimators (DSPECT), Bellevre et al. extracted a planar equivalent image by projecting
and summing all the elementary 2-D images that shared the same angle onto one large field of
view virtual plane (16). After applying a similar correction based on linear regression between
SPECT and planar phantom acquisitions, they found a high agreement between 123
I-MIBG HMR
56
10
obtained using CZT and that obtained using planar imaging. In contrast, the moderate concordance
between cHMRreproj and HMRplanar we found using anterior reprojection images is likely related to
the multi-pinhole collimation, which is responsible for (i) a truncation artifact (31) that interferes
with the mean counts of the myocardial ROI (see Figure 5) and for (ii) a larger non-uniformity
with the DNM-530c compared with Anger camera (31). This limitation was overcome by using
reconstructed transaxial images instead of reprojection images for the measurement of corrected
123I-MIBG HMR with the DNM-530c in our population.
Dual-isotope Acquisition
In our study, we performed simultaneous dual-isotope DNM-530c acquisitions with
99mTc-tetrofosmin (358±177 MBq) and
123I-MIBG(191±29 MBq). This dual-isotope acquisition
allowed the simultaneous assessment of cardiac innervation and function. A previous phantom
study demonstrated that under simultaneous dual-isotope condition, the presence of 123
I did not
impact on LVEF assessment within the 99m
Tc energy window for both dedicated CZT cameras
(22). In addition, a simultaneous dual-isotope protocol provides a clearer 99m
Tc-tetrofosmin image
and a perfect registration to define the heart contours on the 99m
Tc-tetrofosmin image and then
accurately measure 123
I-MIBG heart uptake (16). As shown in Figure 2, the amount of 99m
Tc
activity impacts on 99m
Tc/123
I ratio but does not interfere with the energy resolution of the detector,
modifying only the magnitude but not the width of the photopeak.
Finally, acquisition of both SPECT and planar images using Anger camera usually
requires 30-45 min compared with 10 min using CZT cameras, which is much more convenient
in patients with heart failure.
Study Limitations
Because of the narrow field of view, the cardiac acquisition does not encompass the upper
mediastinum. Consequently, the mediastinal ROI/VOI is positioned in the middle mediastinum on
DNM-530c images, while the mediastinal ROI is set on the upper mediastinum when using a
conventional Anger camera (7). On the other hand, the size and placement (manual or automated)
of the left ventricular ROI does not affect the delayed HMR of 123
I-MIBG using conventional
planar imaging (8). Therefore, further studies are needed to standardize the placement of the
mediastinal ROI or VOI using the different models of available cardiac CZT cameras, at best with
standardized HMR using cross-calibrated conversion coefficients (30). Finally, dual-isotope
acquisition increases the radiation burden. In this retrospective study, the injected 99m
Tc-
57
11
tetrofosmin activity was gradually decreased over time as it became clear that CZT camera allows
the injection of small amounts of perfusion tracer without compromising image quality.
CONCLUSION
This study demonstrated that determination of late HMR of cardiac 123
I-MIBG uptake
using dual-isotope (123
I and 99m
Tc) acquisition on a multi-pinhole CZT camera (DNM-530c) is
feasible in patients with heart failure. However, this determination might be performed using
transaxial reconstructed images and a linear correction based on phantom data acquisitions.
FINANCIAL SUPPORT
No
DISCLOSURE
Tanguy Blaire: no disclosure
Alban Bailliez: no disclosure
Fayçal Ben Bouallegue: no disclosure
Dimitri Bellevre: no disclosure
Denis Agostini: no disclosure
Alain Manrique: no disclosure
COMPLIANCE WITH ETHICAL STANDARDS
Ethical Approval
All procedures performed in studies involving human participants were in accordance
with the ethical standards of the institutional and/or national research committee and with the
principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical
standards.
Informed Consent was obtained from all individual participants included in the study.
ACKNOWLEDGMENTS
Amélie Lansiaux, Sylvie Petit, Mathilde Thélu, and the nuclear medicine technicians at Lille for
their technical assistance.
58
12
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FIGURES AND TABLES
FIGURE 1 Imaging study protocol. The first acquisition is a single-isotope planar acquisition,
using a conventional camera, whereas the second is a dual-isotope acquisition, using a CZT
camera.
FIGURE 2 Single 123
I (24 MBq), single 99m
Tc, and simultaneous (123
I and 99m
Tc) energy spectra
using linear sources and DNM-530c. Notice the low tailing effect and the down-scatter of 123
I
towards 99m
Tc (and the absence of 99m
Tc scatter towards 123
I) in the dual-isotope condition,
whatever the ratio of 99m
Tc:123
I activity; 0.5:1 (A), 1:1 (B), and 5:1 (C) respectively.
123I and 99mTc99mTc123I
Norm
alis
ed c
ounts
Energy (keV)
0
20
40
60
80
100
30 80 130 180
Norm
alis
ed c
ounts
Energy (keV)
Norm
alis
ed c
ounts
0
20
40
60
80
100
30 80 130 180
Energy (keV)
0
20
40
60
80
100
30 80 130 180
A B C
D
0.5 1.0 1.5 2.0
0.5
1.0
1.5
2.0
HMRplanar
HM
Rre
pro
j
Line of perfect concordance
Reduced major axis
CCC: 0.24 (95% CI 0.13 - 0.34)
A
0.5 1.0 1.5 2.0
0.5
1.0
1.5
2.0
HMRplanar
cH
MR
rep
roj
Line of perfect concordance
Reduced major axis
CCC: 0.49 (95% CI 0.32 - 0.63)
C
B
0.5 1.0 1.5 2.0
-0.5
0.0
0.5
1.0
Mean HMR [(HMRplanar + HMRreproj)/2]
Diffe
ren
ce
HM
R [
HM
Rp
lan
ar
- H
MR
rep
roj]
Mean difference : 0.33 (95% CI: 0.07 ; 0.58)
+/- 2SD
y = -0.36 x + 0.783 ; r2
= 0.194
0.5 1.0 1.5 2.0
-0.5
0.0
0.5
1.0
Mean HMR [(HMRplanar + cHMRreproj)/2]
Diffe
ren
ce
HM
R [H
MR
pla
na
r -
cH
MR
rep
roj]
Mean difference : -0.11 (95% CI: -0.29 ; 0.08)
+/- 2SD
y = 0.445 x -0.769 ; r2
= 0.278
0.5 1.0 1.5 2.0
0.5
1.0
1.5
2.0
HMRplanar
HM
Rtr
an
sa
xia
l
Line of perfect concordance
Reduced major axis
CCC: 0.61 (95% CI 0.52 - 0.69)
D
A
0.5 1.0 1.5 2.0
0.5
1.0
1.5
2.0
HMRplanar
cH
MR
tra
nsa
xia
l
Line of perfect concordance
Reduced major axis
CCC: 0.92 (95% CI 0.85 - 0.96)
C
B
0.5 1.0 1.5 2.0
-0.5
0.0
0.5
1.0
Mean HMR [(HMRplanar + HMRtransaxial)/2]
Diffe
ren
ce
HM
R [H
MR
pla
na
r -
HM
Rtr
an
sa
xia
l]
Mean difference : 0.09 (95% CI: -0.34 ; 0.52)
+/- 2SD
y = -0.834 x + 1.27 ; r2
= 0.873
0.5 1.0 1.5 2.0
-0.5
0.0
0.5
1.0
Mean HMR [(HMRplanar + cHMRtransaxial)/2]
Diffe
ren
ce
HM
R [H
MR
pla
na
r -
cH
MR
tra
nsa
xia
l] Mean difference : -0.01 (95% CI: -0.12 ; 0.09)
+/- 2SD
y = 0.006 x -0.022 ; r2
= 0
FIGURE 3 Lin’s concordance correlation
coefficient plots (A, C) and Bland-Atman plots
(B, D) showing the agreement between
HMRreproj and HMRplanar (A, B) and between
cHMRreproj and HMRplanar (C, D).
FIGURE 4 Lin’s concordance correlation
coefficient plots (A, C) and Bland-Atman plots
(B, D) showing the agreement between
HMRtransaxial and HMRplanar (A, B; p<0.01) and
between cHMRtransaxial and HMRplanar (C, D)
62
17
FIGURE 5 Patient #4 with ischemic heart failure (LVEF 44%). HMRs calculated with conventional
planar imaging (HMRplanar= 1.38, A) and using DNM-530c with anterior reprojection images
(HMRreproj= 0.96, E) and with transaxial reconstructed images (HMRtransaxial= 1.2, C, F). The 99m
Tc
image allows positioning on the heart of the ROI (D) or the VOI (B), and is pasted onto the 123
I image
(E and C respectively). Mediastinum VOI on 123
I acquisition (F). HMRreproj and HMRtransaxial were
decreased compared to HMRplanar. Lung activity (red arrows) and truncation artefacts (blue arrows) are
close to the heart.
TABLE 1 HMRs from phantom acquisitions
Heart activity (MBq) HMRplanar HMRreproj HMRtransaxial
1.75 3.56 5.33 6.49
1.5 3.34 4.82 5.77
1.25 2.88 3.84 4.60
1.1 2.77 3.73 4.90
0.94 2.41 2.50 3.81
0.75 2.29 2.14 3.35
0.5 1.86 1.69 2.33
0.35 1.61 1.57 1.65
0.25 1.48 1.34 1.49
0.1 1.21 1.26 0.73
Mean±SD 2.34±0.8 2.82±1.5 3.51±1.94
63
19
TABLE 2 Patients characteristics Case
#
Age Gender Heart failure NYHA1 LVEF Administered dose
(MBq)
HMR
class (%) 123
I-MIBG 99m
Tc-tetrofosmin
Planar Reproj Trans cReproj cTrans
1 70 M ICM II 36 196 241 1.54 1.23 1.48 1.6 1.51
2 67 M ICM III 20 181 222 1.41 1.12 1.36 1.55 1.46
3 65 F NICM II 30 151 264 1.23 0.83 0.88 1.41 1.26
4 77 M NICM I 44 125 370 1.38 0.96 1.2 1.48 1.4
5 82 M NICM I 44 181 265 1.35 1.04 0.99 1.51 1.31
6 67 M ICM II 32 206 282 1.37 0.85 1.18 1.42 1.38
7 79 M ICM I 34 212 245 1.53 1.38 1.42 1.68 1.48
8 75 M ICM II 33 199 109 1.41 1.21 1.17 1.59 1.38
9 73 M ICM II 45 204 632 1.48 1.02 1.47 1.5 1.51
10 78 M ICM I 44 186 271 1.39 1.09 1.52 1.54 1.53
11 67 M NICM II 40 154 734 1.54 1.13 1.6 1.56 1.56
12 81 M NICM II 40 183 276 1.36 1.0 1.5 1.49 1.52
13 69 F NICM I 40 192 578 1.48 1.12 1.47 1.55 1.51
14 85 M ICM I 40 212 225 1.56 1.1 1.68 1.54 1.59
15 78 M ICM I 45 200 176 1.0 0.48 0.22 1.24 0.99
16 64 M NICM III 20 189 232 1.57 1.28 1.78 1.63 1.63
17 76 M ICM I 36 189 525 1.63 1.18 1.73 1.58 1.61
18 58 M NICM III 24 125 370 1.36 1.06 1.02 1.52 1.32
19 70 M NICM II 35 119 880 1.63 1.6 1.84 1.79 1.66
20 59 M ICM I 35 221 290 1.35 1,00 1.02 1.49 1.32
21 60 M ICM II 31 193 549 1.32 0.98 0.97 1.48 1.3
22 82 M NICM II 32 175 528 1.65 1.17 1.89 1.58 1.68
23 55 M NICM II 35 204 263 1.53 1.26 1.52 1.62 1.52
24 70 M ICM II 35 196 288 1.28 0.92 1.23 1.45 1.41
25 77 M NICM III 29 191 225 1.48 1.03 1.38 1.51 1.47
26 80 M ICM II 30 223 267 1.35 1.06 1.04 1.52 1.33
27 68 M ICM II 35 152 263 1.37 1.11 1.36 1.55 1.46
28 80 M ICM II 30 188 302 1.32 1.2 1.26 1.59 1.42
29 67 M NICM II 33 199 335 1.48 1.22 1.37 1.6 1.47
30 71 M ICM II 35 216 308 1.31 0.99 1.11 1.49 1.36
31 70 M ICM II 40 214 275 1.26 1.19 1.1 1.58 1.35
32 70 F NICM II 33 197 597 1.42 1.09 1.39 1.53 1.47
33 72 F ICM I 33 222 235 1.64 1.08 1.74 1.53 1.62
34 54 M ICM II 30 181 317 1.44 1.33 1.24 1.65 1.41
35 59 F NICM I 42 206 326 1.28 0.91 1.02 1.45 1.32
36 60 F NICM I 45 205 377 1.57 1.1 1.69 1.54 1.6
37 72 M NICM III 20 247 295 1.45 1.2 1.11 1.59 1.36
38 77 M NICM II 32 225 345 1.47 1.06 1.29 1.52 1.43
39 59 M ICM II 40 174 294 1.69 1.48 1.95 1.73 1.7
40 59 M ICM I 40 198 720 1.57 1.38 1.67 1.68 1.59
Mean
±SD
71±
9
35±9 191±41 358±177 1.44±0.14 1.12±0.19 1.35±0.34 1.54±0.09 1.45±0.14
1 New York Heart Association functional class.
64
ORIGINAL ARTICLE
First determination of the heart-to-mediastinum ratio usingcardiac dual isotope (123I-MIBG/99mTc-tetrofosmin) CZT imagingin patients with heart failure: the ADRECARD study
Dimitri Bellevre1 & Alain Manrique1,2 & Damien Legallois2,3 & Samy Bross4 &
Rafael Baavour4 & Nathaniel Roth4& Tanguy Blaire2,5 & Cédric Desmonts1 &
Alban Bailliez2,5 & Denis Agostini1,2
Received: 26 March 2015 /Accepted: 10 July 2015# Springer-Verlag Berlin Heidelberg 2015
Abstract
Purpose Cardiac innervation is assessed using the heart-to-
mediastinum ratio (HMR) of metaiodobenzylguanidine
(MIBG) on planar imaging using Anger single photon emis-
sion computed tomography (A-SPECT). The aim of the study
was to determine the HMR of MIBG obtained using a CZT-
based camera (D-SPECT; Spectrum Dynamics, Israel) in
comparison with that obtained using conventional planar
imaging.
Methods The ADRECARD study prospectively evaluated 44
patients with heart failure. They underwent planar acquisition
using the A-SPECT camera 4 h after 123I-MIBG injection
(236.4±39.7 MBq). To localize the heart using D-SPECT,99mTc-tetrofosmin (753±133 MBq) was administered and du-
al isotope acquisition was performed using the D-SPECT sys-
tem. HMR was calculated using both planar A-SPECT imag-
ing and front view D-SPECT cine data. In a phantom study,
we estimated a model fitting the A-SPECT and the D-SPECT
data that was further applied to correct for differences between
the cameras.
Results A total of 44 patients (39 men and 5 women, aged 60
±11 years) with ischaemic (31 patients) and nonischaemic (13
patients) cardiomyopathy completed the study. Most patients
(28 of 44) were NYHA class II, and the mean left ventricular
ejection fraction was 33±7 %. The mean HMR values were
1.34±0.15 and 1.45±0.27 from A-SPECT and D-SPECT, re-
spectively (p<0.0001). After correction, Lin’s concordance
correlation showed an almost perfect concordance between
corrected D-SPECT HMR and A-SPECT HMR, and Bland-
Altman analysis demonstrated a high agreement between the
two measurements.
Conclusion The ADRECARD study demonstrated that deter-
mination of late HMR during cardiac MIBG imaging using
dual isotope (123I and 99mTc) acquisition on a CZTcamera (D-
SPECT) is feasible in patients with heart failure. A linear
correction based on the phantom study yielded a high agree-
ment between 123I MIBG HMR obtained using a CZTcamera
and that from conventional planar imaging.
Keywords CZT . D-SPECT .MIBG . Heart-to-mediastinum
ratio . Heart failure . Dual isotope
Introduction
Impairment of cardiac sympathetic innervation assessed with123I-metaiodobenzylguanidine (MIBG) is recognized as an
independent prognostic factor in patients with heart failure
[1–6]. In a recent multicentre study, the late heart-to-
mediastinum ratio (HMR) was found to be the most important
parameter allowing the classification of patients with heart
failure according to their risk of sudden death and a cardiac
event applying a threshold of 1.6 between low risk and high
risk [6]. Currently, the calculation of HMR requires a planar
static image of the thorax. This technique is well-standardized
and reproducible using Anger SPECT (A-SPECT) [7, 8]. Re-
cently, dedicated cardiac SPECTcameras using CZT detectors
* Denis Agostini
1 Department of Nuclear Medicine, CHU Côte de Nacre, Caen, France
2 EA 4650, Normandie Université, Caen, France
3 Cardiology Department, CHU Côte de Nacre, Caen, France
4 Spectrum Dynamics, Biosensors, Caesarea, Israel
5 Nuclear Medicine Department, IRIS, Polyclinique du Bois,
Lille, France
Eur J Nucl Med Mol Imaging
DOI 10.1007/s00259-015-3141-3
VI. :Premièredéterminationdurapportcardiomédiastinal
en imagerieCZTcardiaquedouble-isotope (123I-MIBG/99mTc-
tétrofosmine) chez les patients porteurs d’insuffisance
cardiaque : l’étudeADRECARD (Eur JNuclMedMol Imaging
2015)
65
VII. :Discussion
A. Principauxrésultats
1. EvaluationdelaFEVGenconditiondouble-isotope
Nosrésultatsontdémontrélafaisabilitédel'évaluationdelaFEVGenutilisantla
TEMPdeperfusionsynchroniséeàl’ECGavecdescamérasCZT.Encequiconcerneles
acquisitionssimultanéesdouble-radiopharmaceutique,l’acquisitiondanslephotopicdu
99mTcn'apasétéaffectéeparleseffetsdudiffuséetdelacontaminationcroiséedel’123I.
Ànotreconnaissance, il s'agitde lapremièreétudesur fantômecardiaquedynamique
synchronisé en double-isotope (99mTc et 123I) évaluant la fonction ventriculaire en
comparantlesdeuxcamérasCZTdisponiblesdanslecommerce(DNM530cetDSPECT).
NosrésultatsontégalementdémontréquelaDNM530cfournissaitdesvolumes
systoliquesplusélevésparrapportàlaDSPECT.Ceteffetdelacamérasurl'évaluationdu
volumeestprobablementliéàlarésolutionspatiale.Imbertetal.(42)ontrapportéles
mesuressuivantesdelarésolutionspatialecentrale:DNM530c(6,7mm)etDSPECT(8,6
mm). Ces résultats concordent avec les résultats précédents de Bailliez et al (40) qui
montraient à la fois chez les fantômes et les patients que les volumes ventriculaires
gauches étaient plus élevés avec la DNM530c qu’avec la DSPECT et la caméra Anger
équipéedecollimateurscardiofocaux.
2. Evaluation de la perfusion (99mTc) en condition double-isotope
(99mTcet123I)
Cetteétudesurfantômeaétéconçuepourimiterl'évaluationcombinéeendouble-
isotopedelaperfusion(99mTc)etdel'innervation(123I)duventriculegaucheaumoyen
d'unfantômedetorseanthropomorpheéquipéd’uninsertcardiaque,enutilisantlesdeux
gamma-caméras à semi-conducteurs CZT dédiées aux explorations cardiaques
disponibles dans le commerce. Bien qu'il y ait eu un effet significatif de l'acquisition
double-isotopesurl'activité99mTc,nosrésultatsontdémontréquelatailledesdéfautsen
66
123I et 99mTc ainsi que leur discordance n'étaient impactées ni par le type de caméra
(DSPECTvs.DNM530c)niparlemoded'acquisition(simpleoudouble-isotope).Ànotre
connaissance,ils'agitdelapremièreétudesurfantômedetorseanthropomorphiqueen
double-isotopeévaluantlaperfusion(99mTc)etl'innervation(123I)enutilisantlesdeux
gamma-caméras à semi-conducteurs CZT dédiées aux explorations cardiaques
disponibles dans le commerce (DNM 530c et DSPECT). Nos résultats rapportent
également que la présence d’123I lors d'une acquisition double-isotope 123I-99mTc ne
compromettaitpasl'évaluationdelaperfusionmyocardiquecentréesurlephotopicdu
99mTcparrapportàuneacquisitionsimple-isotopede99mTc.
3. EvaluationduRCMaveclaDNM530c
a) Synthèsedesrésultats
La réalisation du rapport cardiomédiastinal (RCM) effectué sur l’acquisition
tardive en 123I-MIBG d’une gamma-caméra conventionnelle est bien standardisé. Sa
valeur pronostique est largement reconnue. Dans cette étude rétrospective, effectuée
aveclaDNM530c,chezdespatientssouffrantd'insuffisancecardiaqueàfaibleFEVG,nous
avonscalculéleRCMdelacaptationdel’123I-MIBG.Ànotreconnaissance,ils'agitdela
première étude en double-isotope à évaluer l’innervation cardiaque et la fonction
ventriculairegauchedansl’insuffisancecardiaqueencombinantlaprésenced’123I-MIBG
(191±29MBq)etde99mTc-tétrofosmine(358±177MBq),avecunegamma-caméraà
semi-conducteursCZTàgéométried’acquisitionmulti-sténopée,dédiéeauxexplorations
cardiaques.
LesRCMtardifsdespatientsétaientsignificativementplusfaiblesenimagerieCZT
qu’enimagerieplanaireconventionnelle,maisavecunfortagrémentavecleRCMtransaxial
corrigé.Nosrésultatssontcompatiblesaveclesrésultatsprécédentsdel'étudeAdrecard
(37)réaliséeenutilisantl’autremodèledegamma-caméraCZTdédiéeauxexplorations
cardiaquesavecunerésolutionspatiale,unesensibilitéetunecollimation(parallèlevs
sténopée)différentes(1,2).
67
b) Comparaison des RCM : acquisitions conventionnelles
(planaire)vsDNM530c(planaireetTEMP)
Toutd'abord,afindemieuxcomprendrelescaractéristiquesdesTEMPeffectuées
sur la DNM 530c dans l'imagerie 123I-MIBG, nous avons comparé les acquisitions de
fantômes effectuées sur une gamma-caméra conventionnelle (acquisitions planaires
conventionnelles)surlaDNM530c(acquisitionsTEMP).LesRCMnoncorrigésobtenus
aveclaDNM530contsous-estimélesvaleursfaiblesetsurestimélesvaleursélevéesde
fixation de 123I-MIBG. En conséquence, les valeurs de RCM chez les patients étaient
significativementplusfaiblesaveclaDNM530cqu’aveclacaméraAnger,carcespatients
atteintsd'insuffisancecardiaqueavaientunefixationdiminuéed’123I-MIBG.
c) Nécessitéd’unfacteurdecorrection
Lescollimateursutilisésetlapuissanced'arrêtdumatériaududétecteurpeuvent
avoiruneincidencesurlavaleurduRCMd’123I-MIBG(69,85).Inoueetal.(86)arapporté
qu'un facteur de correction était nécessaire pour améliorer la normalisation entre les
valeursdeRCMobtenuesd’uncollimateurmoyenneénergieetbasse-à-moyenneénergie.
Nakajima et al. a démontré que l'équation de régression linéaire entre les
collimateurs basse-énergie etmoyenne-énergie obtenue lors d’une étude sur fantôme
peutêtreutiliséepournormaliserlamesureduRCMdansl'imagerie123I-MIBG(87-89).
Dansnotreétude,aprèslacorrection,ilyavaitencoreunedifférencesignificativeentre
leRCMreprojectioncorrigéetRCMplanaire(p<0,0001),maisiln'yavaitaucunedifférenceentrele
RCMtransaxialcorrigéetleRCMplanaire(p=NS).
4. EvaluationduRCMaveclaDSPECT
a) Synthèsedesrésultats
En utilisant l’autre modèle de gamma-caméra à semi-conducteurs dédié aux
explorations cardiologiques équipé de colonnes de détecteurs CZT mobiles et d’une
collimation parallèle de tungstène (la DSPECT), Bellevre et al. ont extrait un
68
planogramme, équivalent d’image planaire en reprojetant et en sommant toutes les
imagesélémentaires2-Dquiontpartagélemêmeanglesurungrandplandevuevirtuel
(37).Aprèsl’utilisationd’unecorrectionidentiquebaséesurunerégressionlinéaireentre
lesacquisitionsdefantômeplanairesetTEMP,ilsonttrouvéunagrémentélevéentrele
RCMd’123I-MIBG obtenu en utilisant laDSPECT et celui obtenu en utilisant l'imagerie
planaireconventionnelle.
Ce protocole d’acquisition en double-isotope simultané fournit une image plus
nette de 99mTc-tétrofosmine et une acquisition parfaite pour définir les contours
cardiaques sur l'image de 99mTc-tétrofosmine, puismesurer avec précision la fixation
cardiaqued’123I-MIBG(37).
b) DiscordancedesRCMentrelaDSPECTetlaDNM530c
Enrevanche,laconcordancemodéréeentreleRCMreprojectioncorrigéetleRCMplanaire
que nous avons trouvé en utilisant les images de reprojection antérieure est
vraisemblablement liée à la collimation multi-sténopée, qui est responsable (i) d'un
artefact de troncature (65) qui interfère avec le nombre de coupsmoyendans laROI
myocardique(voirlafigure5)et(ii)d’unenon-uniformitéduchampd’acquisitionplus
grandeaveclaDNM530cqu’aveclacaméraAnger(65).
Cettelimitationaétésurmontéeenutilisantlesimagestransaxiales(RCMtransaxial)
reconstruitesaulieudesimagesdereprojection(RCMreprojection)pourlamesureduRCM
d’123I-MIBGcorrigéaveclaDNM530cdansnotrepopulation.
B. Discussiongénérale
1. Intérêtdesacquisitionsendouble-isotope
En routine clinique, l'acquisition simultanée en double-radiopharmaceutique
permet d'obtenir des images fonctionnelles parfaitement co-enregistrées en un temps
réduit d'imagerie. Avec les caméras conventionnelles d’Anger, plusieurs protocoles
d'imagerie TEMP en double-radiopharmaceutique ont été proposés. L'imagerie
69
simultanée99mTc-sestamibi/123I-BMIPPaétéutiliséepourévaluerlaperfusionderepos
etlemétabolismedesacidesgrassimultanémentchezlespatientsatteintsd'infarctusdu
myocarde récent (90,91). L’usage des caméras conventionnelles d’Anger est bien
documentéetlargementvalidé,dansl'acquisitionsimultanéedouble-isotopeavecle201Tl
etla123I-MIBG,aveclapossibilitédecorrectiondeseffetsdediffuséetdelacontamination
croisée (34), en utilisant notamment la méthode de correction de triple fenêtrage
énergétique(75).
Une étude combinée (séquentielle) de la perfusion puis de l’innervation
sympathique avec des radiopharmaceutiques marqués au 99mTc puis à la 123I-MIBG
permetd'évaluerlesdiscordancesinnervation-perfusionetpeutfournirdesinformations
précieuses pour cibler la zone gâchette dans l’étude de l'arythmie ventriculaire du
myocardeinfarci(21,92).EnutilisantlaDNM530clorsd’uneétudeséquentielleenTEMP
myocardique à la 123I-MIBG puis à la 99mTc-tétrofosmine, Gimelli et al. (16,17) ont
démontré une association entre la dysinnervation, l’altération de la perfusion
myocardiqueetl’asynchronismemyocardique.
2. Champd’acquisitionlimitédesgamma-camérasCZT
L'acquisitiondouble-isotopeaveclescamérasCZTprésentequelquesdifficultés.
L’altérationdel'innervationmyocardiqueentraîneunefaiblefixationmyocardiquedela
123I-MIBG,nécessitantunprotocoled’acquisitiondouble-isotopepour localiser lecœur
(37).
En raison du petit champ de vue des caméras CZT dédiées aux explorations
cardiaques, une pré-acquisition est obligatoire pour localiser le cœur et centrer
correctementlechampd’acquisitionavantlaréalisationdelaTEMP.Enoutre,laplupart
des patients adressés pour une TEMP à la 123I-MIBG ont une insuffisance cardiaque
d’origineischémique(66%dansl'étudeADMIRE-HF(28)).Danscecontexteclinique,le
protocole double-isotope permet un co-enregistrement simple et efficace des études
d'innervation(123I-MIBG)etdeperfusion(99mTc-tétrofosmine),etdoncuneévaluation
robuste de la discordance innervation-perfusion. L’étude de la fonction ventriculaire
gauche,del'innervationetdelaperfusiondumyocardeestuneétapeclédansl'évaluation
dupronostic.Enraisondeseffetsdediffusé,decontaminationcroiséeetdetrainéede
70
l’123Iverslephotopicdu99mTcdesgamma-camérasCZT,cetteétudepourrait-êtrealtérée
parl’utilisationd’unprotocoled’acquisitionendouble-isotopesimultanée.
3. Rapportsdeconcentrationdesisotopes123Iet99mTcenacquisition
double-isotope
Lerapportentrelesconcentrationsd'activité123Iet99mTcaétéfixéaucoursdece
travailà1:2.Cerapportestreprésentatifdelafaiblefixationmyocardiquedela123I-MIBG
observée chez les patients souffrant d'insuffisance cardiaque. Dans ces conditions,
l'absence de corrections lors de l'utilisation de la DNM 530c n'a pas compromis
l'évaluationdelafonctionventriculairedanslephotopicdu99mTcniaffectél'évaluation
de la taille des défauts de fixation en 99mTc lors des acquisitions double-isotope
simultanée (99mTc-123I) par rapport aux acquisitions simple-isotope en 99mTc. Ces
résultatssuggèrentquelacorrectiondeseffetsdediffusé,decontaminationcroiséeetde
trainée vers les basses énergies de l’123I dans le photopic de 99mTc n'a probablement
qu'unepertinencecliniquelimitéechezlespatientsatteintsdecardiopathieischémique.
Sur la DSPECT, la correction de l’effet de trainée n’est effectuée que lors des
acquisitions double-isotope (et non simple-isotopes) (71). Ceci pourrait expliquer la
différencedecontrasted'imageentrelesacquisitionssimple-isotope(acquisitions123Iet
99mTc séquentielles) et les acquisitions double-isotope (123I et 99mTc simultanée)
rapportéedansnotre2èmepartie.Lecontrastedanslessériesd’imagesétaiteneffetplus
élevélorsdesacquisitionssimultanéesdouble-isotopes(123Iet99mTc)aveclaDSPECTque
lorsdesacquisitionssimple-isotopes.
4. Post-traitementdesacquisitionsdouble-isotope:particularitésdes
artefacts
Malgré une augmentation significative de la résolution et de la sensibilité de
l'énergie,lafractiondediffuséaveclacaméraCZTestencoreélevée,évaluéejusqu'à30%
contre34%aveclescamérasconventionnellesAnger(2).Enraisond’unecollectionde
chargeimparfaiteetdudiffuséinter-cristal,lesdétecteursCZTsontsoumisàuneffetde
trainéeàlapartieinférieureduphotopicquipeutconduireàunecorrectionexcessivedes
71
photonsdiffuséssilaméthodeclassiquedefenêtrageàtripleénergie(71)étaitutilisée.
Récemment,Fanetal.pourlaDNM530c(84)etHolstenssonetalpourlaDSPECT(84)
ontprésentéunalgorithmedecorrectionbasésurlagéométried’acquisitiondechaque
modèle.Cetalgorithmeextraitlesphotonsprimairesutilesde99mTcet123Iàpartirdes
donnéesdeprojection,entenantcomptedeseffetsdetrainéepourcorrigerleseffetsdu
diffuséetdelacontaminationcroiséedansl'imageriedouble-isotope99mTc-123I.
Dansnostravaux,touteslesreconstructionsontétéeffectuéesàl'aidedelastation
detraitementetdeslogicielsdisponiblesfournisparlesindustrielsdechaquecaméra.En
routine,lacorrectiondeseffetsdediffusé,decontaminationcroiséeetdetrainéeversles
basses énergies (84) n’est pas disponible pour la DNM 530c. Cette correction est par
contreeffectuéepourlesacquisitionseffectuéessurlaDSPECTenutilisantuneméthode
décriteprécédemment(71).
5. Contaminationcroiséedu99mTcdanslephotopicdu123I
Lacontaminationcroiséede99mTcdanslafenêtredel’123Iestnégligeablelorsde
l'acquisition simultanée de CZT (71). Comme lemontre la figure 2 (article 3, JNM), la
quantitéd'activitéde99mTcaunimpactsurlerapportde99mTc/123Imaisn'interfèrepas
aveclarésolutiond'énergiedudétecteur.Ellenemodifiequelagrandeurduphotopic,
maispassalargeur.
6. Comparaison des durées d’acquisition : gamma-caméra
conventionnellevsCZT
Enfin,l'acquisitiondelaTEMPetdesimagesplanairesenutilisantlacaméraAnger
requierthabituellement30à45minutesversus10minenutilisantdescamérasCZT,ce
quiestbeaucouppluspratiquechezlespatientssouffrantd'insuffisancecardiaque.
72
C. Limitesdenostravaux
1. Valeurréelledesvolumescavitairesinconnue
Enraisondelaconceptiondufantômedynamique(AGATE),lesVTSetVTDn'ont
pasétéprédéterminés.Lefantômeaétéremplidansdesconditionsd'équilibrestatique
aveclapressionatmosphériquepourfournirunefractiond'éjectionreproductible.Surla
basedecetéquilibre,lafractiond'éjectionaétéimposéeeninjectantunvolumedecourse
danslacavitéventriculaire(40,93).Enconséquence,lesvraisVTSetVTDn'étaientpas
connusetnepouvaientdoncpasêtrecomparéauxvolumesmesurés.
2. Différencedepost-traitemententrelesdeuxgamma-camérasCZT
Comme les reconstructions ont été effectuées selon les recommandations de
chaquefabricant,aveclepost-traitementinstalléenconditionderoutine,lescorrections
des effets de diffusé, de contamination croisée et de trainée vers les basses énergies
n’étaienteffectuéesqu’avec laDSPECT,enacquisitiondouble-isotope,maispasavec la
DNM530c.Cependant,nosrésultatsn'ontmontréaucunedifférencesignificativedans
l'évaluation des images 99mTc, entre les conditions d’acquisitions simple-isotope et
double-isotope,mêmeaveclaDNM530c.
Aumieux, la démonstration pourrait être effectuée en comparant les résultats
obtenus avec et sans corrections des effets de diffusé, de contamination croisée et de
trainée vers les basses énergies (84). Cependant, l'objectif de notre étude était de
comparer les résultats obtenus avec les deux caméras CZT en utilisant les logiciels
constructeursdisponiblessurlemarchépourimiterlesconditionsderoutineclinique.
3. Champd’acquisitionlimitédescamérasCZT
Enraisonduchampd’acquisitionétroit,l'acquisitioncardiaquenecomprendpas
lemédiastinsupérieur.Parconséquent,dansnotreétudeclinique(3èmepartiedenotre
travail),laROI(ouVOI)médiastinaleétaitpositionnéeenregarddumédiastinmoyensur
73
lesimagesdelaDNM530c,tandisquelaROImédiastinaleétaitplacéesurlemédiastin
supérieurlorsdel'utilisationd'unecaméraconventionnelleAnger(34).D'autrepart,la
tailleetleplacement(manuelouautomatisé)delaROIcardiaquen'affectentpasleRCM
tardifd’123I-MIBGenutilisantl'imagerieplanaireconventionnelle(35).Parconséquent,
d'autresétudes sontnécessairespournormaliser leplacementde laROIoude laVOI
médiastinaleenutilisantlesdifférentsmodèlesdisponiblesdecamérasCZTdédiéesaux
explorationscardiaques,aumieuxavecunRCMstandardiséenutilisantdescoefficients
deconversiondecalibrationcroisée(87).
4. Irradiationsupplémentairedel’acquisitiondouble-isotope
Enfin, l'acquisition double-isotope augmente la charge d’irradiation. Dans cette
étuderétrospective,l'activitéinjectéede99mTc-tétrofosmineaprogressivementdiminué
dansletemps,carilestdevenuévidentquelacaméraCZTpermettaitl'injectiondepetites
quantitésdetraceursdeperfusionsanscompromettrelaqualitédel'image.
74
ORIGINAL ARTICLE
Segmental and global left ventricular functionassessment using gated SPECT with asemiconductor Cadmium Zinc Telluride (CZT)camera: Phantom study and clinical validation vscardiac magnetic resonance
Alban Bailliez, MD,a,d Tanguy Blaire, MD,a,d Frederic Mouquet, MD, PhD,b
R. Legghe, MD,a B. Etienne, MD,a Damien Legallois, MD,c,d Denis Agostini, MD,
PhD,c,d and Alain Manrique, MD, PhDc,d
a Nuclear Medicine Department, IRIS, Polyclinique du Bois, Lille, Franceb Cardiology, Polyclinique du Bois, Lille, Francec Nuclear Medicine Department, CHU de Caen, Caen, Franced Normandie Universite - EA4650, Caen, France
Received Sep 25, 2013; revised Jan 26, 2014; accepted Feb 17, 2014
doi:10.1007/s12350-014-9899-z
Background. We evaluated gated-SPECT using a Cadmium-Zinc-Telluride (CZT) camera
for assessing global and regional left ventricular (LV) function.
Methods. A phantom study evaluated the accuracy of wall thickening assessment using
systolic count increase on both Anger and CZT (Discovery 530NMc) cameras. The refillable
phantom simulated variable myocardial wall thicknesses. The apparent count increase (%CI)
was compared to the thickness increase (%Th). CZT gated-SPECT was compared to cardiac
magnetic resonance (CMR) in 27 patients. Global and regional LV function (wall thickening
and motion) were quantified and compared between SPECT and CMR data.
Results. In the phantom study using a 5-mm object, the regression between %CI and %Th
was significantly closer to the line of identity (y 5 x) with the CZT (R25 0.9955) than the
Anger (R25 0.9995, P 5 .03). There was a weaker correlation for larger objects (P 5 .003). In
patients, there was a high concordance between CZT and CMR for ESV, EDV, and LVEF (all
CCC >0.80, P < .001). CZT underestimated %CI and wall motion (WM) compared to CMR
(P < .001). The agreement to CMR was better for WM than wall thickening.
Conclusion. The Discovery 530NMc provided accurate measurements of global LV func-
tion but underestimated regional wall thickening, especially in patients with increased wall
thickness. (J Nucl Cardiol 2014;21:712–22.)
Key Words: CZT Æ SPECT Æ myocardial perfusion imaging Æ solid-state cardiac camera Æ left
ventricular function Æ wall thickening Æ wall motion Æ cardiac magnetic resonance Æ tetrofosmin
INTRODUCTION
Over the last decade, advances in microelectronics
and improvements in crystal growth have led to the
increased use of Cadmium Zinc Telluride (CZT)
materials in nuclear medicine. These new materials are
capable of using direct photon conversion and provide
high image quality.1 Other attractive features include
increased sensitivity, high energy, high spatial resolu-
tion, and the ability to be used in compact systems. This
novel generation of detectors has led to new solid-state
camera designs that overcome the limitations of con-
ventional Anger systems.2,3 Commercially available
CZT systems have improved sensitivity and spatial
Reprint requests: Alban Bailliez, MD, Nuclear Medicine Department,
IRIS, Polyclinique du Bois, 144 avenue de Dunkerque, 59000 Lille,
France; [email protected]
VIII. :Autrestravaux:Évaluationdelafonctionventriculairesurgamma-camérasàsemi-conducteurs
1. EtudesurfantômeetvalidationcliniquevsIRMdel’évaluationdes
fonctionsventriculairesgauchessegmentaireetglobaleutilisantunegamma-
caméraàsemi-conducteurCZT(JNuclCardiol2014;21:712-22)
75
Doi: 10.2967/jnumed.115.168575Published online: April 28, 2016.
2016;57:1370-1375.J Nucl Med.
Valette and Alain ManriqueAlban Bailliez, Olivier Lairez, Charles Merlin, Nicolas Piriou, Damien Legallois, Tanguy Blaire, Denis Agostini, Frederic Phantom Study and Clinical Validation
-Camera with Cardiofocal Collimators: Dynamic CardiacγCameras Compared with a Left Ventricular Function Assessment Using 2 Different Cadmium-Zinc-Telluride
http://jnm.snmjournals.org/content/57/9/1370This article and updated information are available at:
http://jnm.snmjournals.org/site/subscriptions/online.xhtml
Information about subscriptions to JNM can be found at:
http://jnm.snmjournals.org/site/misc/permission.xhtmlInformation about reproducing figures, tables, or other portions of this article can be found online at:
(Print ISSN: 0161-5505, Online ISSN: 2159-662X)1850 Samuel Morse Drive, Reston, VA 20190.SNMMI | Society of Nuclear Medicine and Molecular Imaging
is published monthly.The Journal of Nuclear Medicine
© Copyright 2016 SNMMI; all rights reserved.
by Alban Bailliez on September 15, 2016. For personal use only. jnm.snmjournals.org Downloaded from
2. Etudesurfantômedynamiqueetvalidationcliniquedel’évaluationde
lafonctionventriculairegaucheutilisantdeuxgamma-camérasCZTdifférentes
etunegamma-caméraàcollimationcardiofocale(JNuclMed.2016;57:1370-
75)
Récompensée en juin 2017 lors de la SNM de Denver : Alavi-Mandell Publication Awards for Articles Published in 2016 (Funded by the ERF)
76
Left Ventricular Function Assessment Using 2 Different
Cadmium-Zinc-Telluride Cameras Compared with a
g-Camera with Cardiofocal Collimators: Dynamic Cardiac
Phantom Study and Clinical Validation
Alban Bailliez1–3, Olivier Lairez4, Charles Merlin5, Nicolas Piriou6, Damien Legallois3,7, Tanguy Blaire1–3,
Denis Agostini3,8, Frederic Valette6, and Alain Manrique3,8
1Nuclear Medicine, IRIS, Polyclinique du Bois, Lille, France; 2Nuclear Medicine, UF 5881, Groupement des Hôpitaux de l’Institut
Catholique de Lille, Lomme, France; 3Normandie Université–EA4650, Caen, France; 4Nuclear Medicine, CHU de Toulouse,
Toulouse, France; 5Nuclear Medicine, Centre Jean Perrin, Clermont-Ferrand, France; 6Nuclear Medicine, CHU de Nantes, Nantes,
France; 7Cardiology, CHU de Caen, Caen, France; and 8Nuclear Medicine, CHU de Caen, Caen, France
This study compared two SPECT cameras with cadmium-zinc-telluride
(CZT) detectors to a conventional Anger camera with cardiofocal collima-
tors for the assessment of left ventricular (LV) function in a phantom and
patients. Methods: A gated dynamic cardiac phantom was used. Eigh-
teen acquisitions were processed on each CZT camera and the conven-
tional camera. The total number of counts within a myocardial volume of
interest varied from 0.25 kcts to 1.5 Mcts. Ejection fraction was set to
33%, 45%, or 60%. Volume, LV ejection fraction (LVEF), regional wall
thickening, andmotion (17-segmentmodel) were assessed. One hundred
twenty patients with a low pretest likelihood of coronary artery disease
and normal findings on stress perfusion SPECT were retrospectively
analyzed to provide the reference limits for end-diastolic volume (EDV),
end-systolic volume (ESV), ejection fraction, and regional function for each
camera model. Results: In the phantom study, for each ejection fraction
value, volume was higher for the CZT cameras than for the conventional
camera, resulting in a decreased but more accurate LVEF (all P ,
0.001). In clinical data, body-surface–indexed EDV and ESV (mL/m2)
were higher for one of the CZT cameras (Discovery NM 530c) than for the
other (D-SPECT) or the conventional camera (respectively, 40.5 ± 9.2,
37 ± 7.9, and 35.8 ± 6.8 for EDV [P , 0.001] and 12.5 ± 5.3, 9.4 ± 4.2,
and 8.3 ± 4.4 for ESV [P , 0.001]), resulting in a significantly decreased
LVEF: 70.3% ± 9.1% vs. 75.2% ± 8.1% vs. 77.8% ± 9.3%, respectively
(P, 0.001). Conclusion: The new CZT cameras yielded global LV func-
tion results different from those yielded by the conventional camera. LV
volume was higher for the Discovery NM 530c than for the D-SPECT or
the conventional camera, leading to decreased LVEF in healthy
subjects. These differences should be considered in clinical practice and
warrant the collection of a specific reference database.
Key Words: CZT; myocardial perfusion imaging; left ventricular
function; wall thickening; dynamic phantom; cardiofocal collimators
J Nucl Med 2016; 57:1370–1375
DOI: 10.2967/jnumed.115.168575
Myocardial perfusion imaging is extensively used in patients
with known or suspected coronary artery disease. In addition, the
measurement of left ventricular (LV) ejection fraction (LVEF), end-
diastolic volume (EDV) and end-systolic volume (ESV) using SPECT
has been widely validated in comparison to other imaging techniques
(1,2) and is commonly used for prognosis assessment and clinical
decision making (3). Moreover, it has been demonstrated that the
reference limits of LV function are sex-specific but do not depend
on type of tracer or acquisition camera when conventional Anger
cameras are used (4), suggesting equivalency for patient management.
Dedicated cadmium-zinc-telluride (CZT) g-cameras revealed a
new step in SPECT myocardial perfusion imaging. These cameras
allow for reduced imaging time (5) and reduced exposure of pa-
tients to radiation (6,7) but are not equivalent in terms of count
sensitivity and spatial resolution, leading to images with differ-
ences in sharpness and contrast-to-noise ratio in clinical practice
(8). Previous publications have validated the performance and
results of these cameras versus the conventional Anger camera
in clinical practice (9,10), but recent data demonstrated that when
quantitative gated SPECT is performed using CZT cameras in-
stead of Anger cameras, LV volume is overestimated, leading to
a lower estimated LVEF in healthy patients (11). This difference is
likely related to the increased spatial resolution, a condition that
also significantly affects the assessment of segmental wall motion
and thickening (12,13). Alternatively, the multifocal collimators of
IQ-SPECT technology (Siemens Healthcare) can be plugged into
multipurpose cameras, offering better sensitivity and contrast-to-
noise ratio than conventional Anger cameras equipped with low-
energy, high-resolution collimators (14).
Because commercially available CZT cameras and IQ-SPECT
cameras have differences in sensitivity and spatial resolution, it
remains unclear whether the type of camera may affect assessment
of LV volume and LVEF. Consequently, the aim of this study was,
first, to perform a head-to-head comparison of two commercially
available CZT cameras versus a conventional Anger camera with
IQ-SPECT collimators in the assessment of LV function on a
dynamic cardiac phantom and, second, to confirm the phantom
results by retrospectively analyzing data from patients with a low
pretest likelihood of coronary artery disease.
Received Oct. 20, 2015; revision accepted Mar. 26, 2016.For correspondence or reprints contact: Alban Bailliez, Nuclear Medicine
Department IRIS, 144 Avenues de Dunkerque, Polyclinique du Bois, 59000Lille, France.E-mail: [email protected] online Apr. 28, 2016.COPYRIGHT © 2016 by the Society of Nuclear Medicine and Molecular
Imaging, Inc.
1370 THE JOURNAL OF NUCLEAR MEDICINE • Vol. 57 • No. 9 • September 2016
by Alban Bailliez on September 15, 2016. For personal use only. jnm.snmjournals.org Downloaded from
77
3. Etudedelafonctionetdel’asynchronismeventriculairedroitet
gauche:comparaisondelatomoventriculographieisotopiqueàla
ventriculographieisotopiqueplanaireavecunegamma-caméraàsemi-
conducteurCZTetavecunegamma-caméraconventionnelle.(Encoursde
soumissionauJNC)
78
IX. :Conclusionetperspectives
A. Conclusion
Notre travail s’est concentré, en condition de routine clinique, sur l’apport de
l’amélioration de la résolution en énergie des deux gamma-caméras à semi-
conducteursdédiéesauxexplorationscardiologiques(DNM530cetDSPECT).Bienque
construitesaveclemêmecristalCZTpixélisé(2,46x2,46mm),cesdeuxgamma-caméras
présententdesdifférencesnotables.
Lasensibilité(x4vsx7)(1,42),larésolutionspatiale(6,7mmvs8,6mm),lagéométrie
d’acquisition(collimationmulti-sténopéestatiquevscollimationparallèlemobile)et le
post-traitement(correctiondeseffetsdediffusé,decontaminationcroiséeetdetrainée
vers les basses énergies absente sur la DNM 530c vs présente uniquement lors des
acquisitionsdouble-isotopesurlaDSPECT)sontdifférents.
Ces deux-gamma-caméras ont fourni des résultats similaires dans les trois
partiesdenotretravail,portantsur:
(i) l'évaluation de la fonction ventriculaire (VTD, VTS et FEVG) lors d’acquisitions
simple-isotope(acquisitions123Iet99mTcséparées)etdouble-isotopesimultanées(123Iet
99mTc);effectuéesurunfantômecardiaquedynamique(94),
(ii) l’étude segmentaire de l'innervation et de la perfusion myocardiques
(concordanceetdiscordance)lorsd’acquisitionssimple-isotope(acquisitions123Iet99mTc
séparées) et double-isotope simultanées (123I et 99mTc), effectuée sur un fantôme
anthropomorphedetorseéquipéd’uninsertcardiaque(95),
(iii) la détermination du RCM tardif de fixation de la 123I-MIBG en utilisant une
acquisitiondouble-isotope (123I et 99mTc) chez lespatientsporteursd’une insuffisance
cardiaque.Cettedéterminationestpossiblesurleplanogramme(DSPECT)(37)etsurles
reconstructions transaxiales (DNM 530c) (95). Une correction linéaire basée sur des
acquisitionsdedonnéesdefantômesestnécessaire.
79
Cesrésultatspeuventavoirdesimplicationsdiagnostiquesetthérapeutiqueschezles
patients atteints d'insuffisance cardiaque adressés dans les services de médecine
nucléairepouruneévaluationcombinéedelaperfusionetdel’innervation.
Parallèlementàcestravaux,nousnoussommeségalementintéressésauxapports
de l’amélioration de la résolution spatiale qu’offraient ces deux gamma-caméras dans
l’étudedelafonctionventriculaire,etavonsparticipéàlarédactionetlapublicationdes
troisétudessuivantes,rapportant:
(i)Lesdifférentescaractéristiquestechniquesdesdeuxgamma-camérasCZTdédiées
aux explorations cardiologiques disponibles dans le commerce et la caméra
conventionnelle équipée d'un collimateur astigmatique ont donné lieu à différentes
estimationsdelafonctionventriculairegauchelorsquelelogicielQGSaétéutilisépourla
détectiondelaparoimyocardiqueen3dimensions.Cesrésultatsconfirmentlanécessité
devaleursderéférenceajustéesausexeetàlagamma-camérapourlesparamètresdela
fonctionventriculairegauche(39).
(ii)L’étudedelaFEVGestsimilaire,avecunetrèsbonneconcordance,entrelaDNM
530cetunegamma-caméraconventionnelle(mêmesilesvolumesventriculairesgauche
et droit sont nettement inférieurs avec la DNM 530c) et que l’on a comparé des
ventriculographiesisotopiquesàl’équilibreetdestomogrammesreprojetésobtenusde
laDNM530c.Cestomogrammesreprojetéspourrait-êtreproposéscommealternativeà
l’acquisition de ventriculographie isotopique à l’équilibre afin d’éviter les acquisitions
planairesadditionnelles(40).
(iii)ParrapportàlacaméraAnger,lacaméraCZTafournidesmesuresprécisesdela
fonctionventriculairegaucheglobaleetaméliorél’étudedel’épaississementdelaparoi
myocardiquechez lespatientsprésentantuneparoiventriculairenormaleouamincie.
Cependant, la résolution spatiale accrue peut entraîner une sous-estimation de
l'épaississement régional de la paroi myocardique dans les parois myocardiques
hypertrophiques. L'analyse de la cinétique segmentaire n'a pas été influencée par
l’amplitude du mouvement et peut être un meilleur outil pour évaluer la fonction
segmentaire du ventricule gauche dans la pratique quotidienne. D'autres études sont
nécessairespouraborderl'impactdelacaméraCZTsurl'évaluationdel'épaississement
80
régionaldelaparoidanslacardiomyopathiehypertrophique.
B. Perspectives
1. Soumissiond’unesynthèsedecetravailencours
Unesynthèsedecetravailestencoursderédactionetdesoumissionavecles
différentsco-auteursdenospublications,danslejournalfrançaisdemédecinenucléaire.
2. Améliorerlepost-traitementdesdeuxgamma-camérasCZT
Effectueretcomparerlareconstructionsanspuisaveclesméthodesdecorrections
récentes des effets de diffusé, de contamination croisée et de trainée vers les basses
énergies,enacquisitiondouble-isotope(123Iet99mTc),avec laDNM530cet laDSPECT
(84,92).
3. Optimiser l’irradiation supplémentaire de l’acquisition double-
isotope
Continuer àoptimiser ladiminutionde l'activité injectéede 99mTc-tétrofosmine
pourlocaliserlecœur,àpartird’acquisitionsdouble-isotope(123Iet99mTc)effectuéesen
mode-list.
Ouaucontraire,administrerunedosed’activitédiagnostiquederoutineclinique
de99mTc-tétrofosminepourétudierlorsd’uneseuleacquisitionendouble-isotope(i)la
perfusionmyocardique,lafonctionventriculairegauche(cinétiquesegmentaire,volumes
ventriculaires gauches et FEVG) sur l’acquisition de 99mTc-tétrofosmine et (ii)
l’innervationcardiaquesurl’acquisitionàla123I-MIBG.
4. Champ d’acquisition limité des gamma-caméras dédiées aux
explorationscardiaques
Continuerd'autresétudescliniquespournormaliserleplacementdelaROIoude
la VOI médiastinale en utilisant les différents modèles disponibles de caméras CZT
81
dédiéesauxexplorationscardiaques,aumieuxavecunRCMstandardiséenutilisantdes
coefficientsdeconversiondecalibrationcroisée(87).
Comparer les valeurs de RCM des études transaxiales (activité moyenne VOI
cardiaque/activitémoyenneVOImédiastinale)delaDSPECTetdelaDNM530c).
5. Gamma-caméraàsemi-conducteurCZTgrandchamp
Notre service Lillois s’équipe en septembre 2017 de laDNM670 CZT, gamma-
caméra grand champ à semi-conducteur (General Electric Healthcare, Milwaukee,
Wisconsin).Cetéquipementdepointe(5èmeserviceéquipéenFrance)nouspermettrade
poursuivrenostravauxinitiésdanslesdomainesextra-cardiologiques.
6. PoursuitedelacollaborationLillo-Caenaise
Ces 5 années de travaux ont permis de créer des liens forts réciproques
scientifiques,confraternelsetamicaux.Noséquipesrespectivesontapprisàtravailleret
àcollaborerensemble,danslerespectmutueletlaconfiance.Noussouhaitonspoursuivre
cettecollaborationettoutesuggestiondeprojetscommuns.
82
X. :Bibliographie
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RESUMELesnouvellesgamma-camérasàsemi-conducteursutilisantdesdétecteursauCZTsontdédiéesaux explorations cardiaques. Leurs sensibilité, résolution spatiale et en énergie nettementaméliorées comparativement aux gamma-caméras conventionnelles sont une révolution enmédecine nucléaire. Ces gamma-caméras utilisent de nouvelles géométries d’acquisition, denouveauxalgorithmesdereconstruction,etouvrentdenouvellesperspectivesdans lesétudessimultanéesendouble-isotopedel’123Ietdu99mTc,dontlespicsénergétiquessontproches.Nous avons étudié l’impact de l’amélioration de la résolution en énergie en comparant deuxmodèles de gamma-caméras à détecteurs semi-conducteurs aux gamma-camérasconventionnelles.Al’aided’étudessurfantômesanthropomorphesetchezdespatientsporteursd’insuffisancecardiaque,notretravails’estconcentrésurlesacquisitionsscintigraphiques(i)delafonctionventriculairegauche(99mTc)enprésenced’123I,(ii)delaperfusionmyocardique(99mTc)en présence d’123I (innervation), et (iii) du rapport cardiomédiastinal de la fixation d’123I-métaiodobenzylguanidine (123I-MIBG) lors d’acquisitions double-isotope (123I-MIBG/99mTc-tétrofosmine)chezlespatientssouffrantd’insuffisancecardiaque.Nosrésultatsmontrentquelameilleurerésolutionenénergiedesgamma-camérasCZTpermeten étude double-isotope (i) une évaluation de la FEVG et du mouvement régional dans lesdifférentesfenêtresd'énergie(123Iou99mTc)etlestypesd'acquisition(simple-vsdouble-isotope),(ii)uneévaluationsimultanéeetcombinéede laperfusion(99mTc)etde l’innervation(123I)dumyocarde,et(iii)l’évaluationdurapportcardiomédiastinaldelafixationd’123I-MIBG.Chacunedecestroispartiesafaitl’objetd’unepublication.Mots-clefs : tellururede cadmium-zinc ; scintigraphie ; double-isotope ; fonction ventriculairegauche;innervationdumyocarde;insuffisancecardiaque;123I-MIBG.
ABSTRACTDual-isotope(123I/99mTc)myocardialSPECTusingsemiconductorgamma-cameras:
methodologicalaspectsandclinicalapplications.
Newdedicated-cardiaccamerasusingCZTdetectorshavedramaticallytransformedtheroutineofmyocardialperfusionimaging.Withabettercountdetectionsensitivity,animprovedspatialandenergyresolution,theypotentiallyenablecombinedassessmentofmyocardialinnervation(123I)andperfusion(99mTc)withinasingleimagingsession.Thesecamerasimageswithdifferentsharpnessandcontrast-to-noiseratios.Using two CZT cameras with anthropomorphic phantom, and clinical studies in heart failurepatients,ourworkfocusedon(i)theleftventricularfunctionassessmentwithinthe99mTcwindowin presence of 123I, (ii) the evaluation of regionalmyocardial innervation (123I) and perfusion(99mTc)matchandmismatchwithsingle-(separate123Iand99mTcacquisition)andsimultaneousdual-isotopeacquisitions,and(iii)thelateheart-to-mediastinalratio(HMR)of123I-MIBGuptakedeterminedusingdual-isotopeCZTacquisitionwiththatdeterminedusingconventionalplanarimaginginpatientswithheartfailure.Ourresultsfoundnoimpactoftheacquisitionmode(singlevsdual)orthetypeofCZTcameraon123Iand99mTcdefectsizeandmismatch,LVEF,andHMRof123I-MIBGuptake.This work provides a new step toward simultaneous dual-isotope acquisition for combinedinnervation,perfusionandventricularfunctionassessment.Keywords:cadmium-zinc-telluride;dual-isotope;123I-MIBG;myocardialinnervation;myocardialperfusion.
